Bacteriophage Applications for Controlling Pathogens in Seafood Processing and Storage

Abstract

Seafood products are highly perishable and particularly susceptible to contamination by pathogenic and spoilage microorganisms, including Listeria monocytogenes, Vibrio spp., Salmonella spp., and Escherichia coli. Conventional control strategies in seafood processing and storage largely rely on chemical preservatives and thermal treatments, which may negatively affect sensory quality and increasingly conflict with consumer demand for minimally processed, “clean-label” foods. In this context, bacteriophages, viruses that specifically infect and lyse bacterial hosts, have emerged as natural, targeted, and environmentally sustainable biocontrol agents for food safety applications. This review provides a comprehensive assessment of bacteriophage applications in seafood processing and storage, with particular emphasis on their mechanisms of action, host specificity, and ability to selectively reduce pathogenic bacteria without compromising nutritional or sensory attributes. Recent advances in phage-based technologies, including phage cocktails, immobilized phage systems, and genetically engineered phages, are discussed in relation to their efficacy against major seafood-associated pathogens under both laboratory and industrial conditions. Key challenges limiting large-scale implementation such as phage resistance development, regulatory considerations, stability during processing and storage, and consumer perception are critically evaluated. In addition, the review highlights emerging evidence on the synergistic use of bacteriophages with complementary preservation strategies, including natural antimicrobials and innovative packaging systems. Overall, this review underscores the potential of bacteriophage-based interventions as practical and sustainable tools to enhance seafood safety, extend shelf life, and support modern seafood processing practices aligned with evolving regulatory and consumer expectations.

1. Introduction

Seafood constitutes a major source of high-quality protein and essential micronutrients in the human diet, and global per capita seafood consumption continues to rise. However, seafood products are inherently vulnerable to microbial contamination throughout harvesting, processing, storage, and distribution due to their high water activity, neutral pH, and nutrient-rich composition [1]. Pathogenic bacteria of particular concern include Listeria monocytogenes, Vibrio parahaemolyticus, Vibrio vulnificus, Salmonella spp., and pathogenic Escherichia coli, all of which have been repeatedly associated with seafood-borne illnesses and product recalls [2,3]. In addition to public health risks, spoilage bacteria such as Pseudomonas spp. and Shewanella spp. contribute significantly to economic losses by accelerating quality deterioration during refrigerated storage [1,4].

Conventional microbial control strategies in seafood processing rely on thermal treatments, salting, smoking, chemical preservatives, and disinfectants. While effective, these interventions may adversely affect sensory quality, nutritional value, and native microbiota, and often conflict with increasing consumer demand for minimally processed and “clean-label” seafood products [5]. Although non-thermal technologies such as high hydrostatic pressure (HHP), pulsed electric fields (PEF), cold plasma, and ozone treatment have shown promise, their industrial application remains limited by high capital costs, operational complexity, and the need for specialized infrastructure [1]. These constraints have driven growing interest in alternative, targeted biocontrol strategies that can enhance seafood safety without compromising product quality.

Bacteriophages, viruses that specifically infect and lyse bacteria, have emerged as a highly selective and environmentally sustainable antimicrobial option in food systems. Bacteriophages offer several distinct advantages over conventional antimicrobial strategies in seafood processing and storage. Their high host specificity enables targeted elimination of pathogenic bacteria without disrupting background microbiota or compromising sensory and nutritional quality, which is a critical consideration for fresh and minimally processed seafood products [6]. Unlike chemical preservatives or thermal treatments, strictly lytic bacteriophages remain active at refrigeration temperatures, allowing continued pathogen suppression throughout cold-chain storage where many seafood-associated pathogens remain metabolically active [7]. In addition, bacteriophages are naturally occurring biological entities ubiquitous in aquatic environments, aligning well with clean-label and sustainability-oriented processing frameworks. Several phage preparations have also received regulatory approval as food processing aids, including GRAS status in the United States for Listeria-specific phages, supporting their practical applicability in seafood systems [8].

Despite these advantages, the application of bacteriophages in seafood systems is associated with important limitations that must be addressed for successful industrial implementation. Their inherently narrow host range requires careful strain selection and, in most cases, formulation of phage cocktails to ensure adequate pathogen coverage in genetically diverse microbial populations commonly encountered in seafood processing environments [9]. The emergence of phage-resistant bacterial strains, although often accompanied by fitness trade-offs, remains a concern, particularly when phages are applied repeatedly or as stand-alone interventions [10,11]. Moreover, phage efficacy can be strongly influenced by seafood matrix characteristics such as surface topology, salinity, pH, and organic matter content, which may limit phage adsorption, diffusion, and overall antimicrobial performance [12]. Additional challenges include heterogeneity in regulatory frameworks across jurisdictions and limited consumer awareness or acceptance related to the use of viruses in food systems, both of which can affect commercial adoption [10,13,14,15].

Recognizing both the advantages and constraints of bacteriophage-based interventions is therefore essential for evaluating their realistic role in seafood safety management. Rather than serving as universal replacements for existing controls, bacteriophages are best positioned as targeted components of integrated, multi-hurdle preservation strategies that complement established sanitation, refrigeration, and process controls to enhance seafood safety while maintaining product quality [10].

Phages exhibit high host specificity, often at the species or strain level, enabling targeted pathogen control in food systems [6,16,17]. Importantly, lytic bacteriophages do not replicate in eukaryotic cells and have been shown to be safe for human consumption, supporting their suitability for food applications. The U.S. Food and Drug Administration has approved several phage preparations as Generally Recognized as Safe (GRAS), including products targeting L. monocytogenes in ready-to-eat foods, further legitimizing their use in food processing environments [8].

Recent research has demonstrated the effectiveness of bacteriophages against key seafood-associated pathogens under both laboratory and applied conditions. Phages and phage cocktails targeting V. parahaemolyticus have been shown to significantly reduce bacterial loads in shrimp, raw fish, squid, oysters, and aquaculture species, while also inhibiting biofilm formation on seafood surfaces and processing equipment [18,19]. Similarly, Listeria-specific phages such as Listex™ P100 (Micreos Food Safety, Wageningen, The Netherlands) and vB-LmoM-SH3-3 (Micreos Food Safety, Wageningen, The Netherlands) have achieved multi-log reductions of L. monocytogenes in raw salmon, fermented fish, and smoked seafood during refrigerated storage, highlighting their potential for post-process contamination control [7,20]. Phage applications have also been explored for Salmonella spp. and spoilage organisms, demonstrating both safety enhancement and shelf-life extension [21,22].

Despite these promising outcomes, several challenges currently limit large-scale industrial implementation of phage-based biocontrol in seafood systems. As comprehensively analyzed by Yan et al. [1], these challenges include phage stability under cold storage and variable pH, the emergence of phage-resistant bacterial strains, potential horizontal gene transfer associated with temperate phages, regulatory heterogeneity across jurisdictions, and limited consumer awareness or acceptance. The complexity of seafood matrices, including high salt content, proteins, and fats, can further influence phage adsorption and efficacy, underscoring the need for matrix-specific optimization strategies.

To address these limitations, recent advances focus on phage cocktails with complementary host ranges, encapsulation and immobilization technologies to improve stability, and synergistic combinations of phages with natural antimicrobials, non-thermal processing, or antimicrobial packaging systems [23]. Such integrated approaches align with modern “hurdle technology” frameworks and offer practical pathways for incorporating phages into existing seafood safety management systems.

Accordingly, this review synthesizes current knowledge on bacteriophage applications for controlling pathogenic and spoilage bacteria in seafood processing and storage. Emphasis is placed on biological mechanisms, formulation strategies, pathogen-specific efficacy, regulatory considerations, and translational challenges. By integrating recent experimental findings with industrial and regulatory perspectives, this review aims to clarify the role of bacteriophage technology as a viable, sustainable biocontrol tool for improving seafood safety and quality.

2. Search Strategy and Literature Selection

This review was conducted using a structured narrative literature search to identify peer-reviewed studies relevant to bacteriophage applications in seafood processing and storage. Electronic databases including Web of Science, Scopus, PubMed, and Google Scholar were systematically searched. The primary search period covered publications from 2005 to 2024, reflecting the period of significant development in food-related bacteriophage research, while earlier foundational studies were included where necessary to provide historical or mechanistic context.

Search queries were constructed using combinations of keywords such as bacteriophage, phage, seafood, fish, shellfish, aquaculture, L. monocytogenes, Vibrio spp., Salmonella spp., E. coli, food safety, biocontrol, processing, storage, packaging, and non-thermal technologies. Boolean operators and database-specific filters were applied to refine search results.

Studies were included if they (i) investigated lytic bacteriophages relevant to food or seafood systems, (ii) reported experimental, applied, or review-level findings on pathogen or spoilage control in seafood matrices, or (iii) addressed technological, formulation, regulatory, or industrial considerations pertinent to seafood preservation. Studies focusing exclusively on therapeutic or clinical phage applications, temperate phages, or non-food environments were excluded unless they provided mechanistic insights directly transferable to food systems. In addition, the reference lists of key review articles were manually screened to identify additional relevant publications.

3. Bacteriophages as Targeted Biocontrol Agents in Seafood Systems

The fundamental antibacterial mechanisms by which lytic bacteriophages inactivate bacterial pathogens, including adsorption, genome injection, replication, host cell lysis, and biofilm disruption. These mechanisms form the basis for the selective and self-limiting antimicrobial activity of bacteriophages in seafood systems.

3.1. Biological and Ecological Characteristics Relevant to Seafood Applications

Bacteriophages are naturally occurring viruses widely distributed in aquatic environments, including marine waters and seafood-associated ecosystems [24]. Their ecological ubiquity in seafood-associated environments provides a strong biological rationale for their use as biocontrol agents in seafood safety management. For food and processing applications, attention is restricted to strictly lytic bacteriophages, which replicate exclusively through bacterial lysis and do not integrate their genetic material into host chromosomes [8]. This distinction is critical, as temperate phages may facilitate horizontal gene transfer and are therefore unsuitable for food safety interventions.

One of the most important features of bacteriophages is their high host specificity, which is often limited to the species or even strain level. In seafood systems, this specificity enables targeted reduction in pathogens such as L. monocytogenes or Vibrio spp. while preserving background microbiota that contribute to product quality and ecological balance [6]. Unlike broad-spectrum antimicrobials, phages exert selective pressure only on susceptible bacteria, thereby reducing the likelihood of unintended effects on non-target microorganisms.

Phage replication is inherently host-dependent, conferring a self-limiting antimicrobial activity. As bacterial populations decline, phage replication decreases correspondingly, preventing uncontrolled accumulation in food matrices. This dynamic behavior differentiates phages from chemical preservatives and supports their compatibility with minimally processed seafood products [24].

From a safety perspective, bacteriophages do not infect eukaryotic cells and are naturally encountered in aquatic and food-associated environments. Lytic bacteriophages have been evaluated for food use, and several phage preparations have received regulatory approval for specific food applications, including approval under the U.S. Food and Drug Administration’s Generally Recognized as Safe (GRAS) framework for control of L. monocytogenes [8]. This regulatory acceptance supports the feasibility of using phages as targeted biocontrol agents in seafood processing and storage environments. It should be noted that regulatory approval is phage- and application-specific rather than universal.

The key biological and functional characteristics of bacteriophages that underpin their suitability for seafood biocontrol applications are summarized in

Table 1. Key characteristics of bacteriophages relevant to their application in seafood safety.

Characteristic	Relevance in Seafood Systems
Strictly lytic life cycle	Ensures bacterial inactivation without genomic integration
High host specificity	Targeted pathogen control with minimal impact on background microbiota
Host-dependent replication	Self-limiting activity as bacterial populations decline
Activity at refrigeration temperatures	Compatibility with cold-chain storage
Antibiofilm potential	Control of persistent contamination on food-contact surfaces

.

3.2. Mechanisms of Antibacterial Activity in Seafood Matrices

The antibacterial action of bacteriophages is initiated by adsorption to specific receptors on the bacterial cell surface, including lipopolysaccharides, outer membrane proteins, flagella, or capsular polysaccharides [25,26]. Following adsorption, phages inject their genetic material into the host cell, redirecting bacterial metabolic pathways toward phage replication. The infection cycle culminates in host cell lysis and release of progeny phages, which can subsequently infect neighboring susceptible bacteria [24].

In seafood systems, the effectiveness of phage-mediated bacterial inactivation is strongly influenced by matrix-dependent factors, including temperature, salinity, pH, water activity, and the physical structure of the food surface. High lipid content, elevated protein levels, and salt concentration can interfere with phage adsorption, diffusion, and host contact, potentially reducing antimicrobial efficacy. As a result, fatty fish products such as salmon may require higher multiplicity of infection or alternative application strategies compared with lean white fish, underscoring the need for matrix-specific optimization in seafood systems.

Seafood products are typically stored under refrigeration, and many seafood-associated pathogens, including L. monocytogenes and V. parahaemolyticus, remain metabolically active at low temperatures. Under these conditions, phage infection can still occur; however, adsorption and intracellular replication processes are generally slowed. Consequently, phage-mediated bacterial reduction at low temperature may reflect delayed replication cycles and cumulative lytic events over extended storage periods rather than the rapid lysis observed at optimal growth temperatures [3,7,27].

Surface topology and moisture content also influence phage efficacy. Effective infection requires sufficient contact between viral particles and bacterial cells, which may be facilitated by the high-moisture environments typical of seafood products [28,29,30]. However, complex food matrices containing proteins, lipids, and salts can interfere with phage adsorption or diffusion, necessitating matrix-specific optimization of application methods, doses, and contact times. Beyond planktonic populations, these considerations are particularly relevant in structured biofilm communities commonly encountered in seafood processing environments, where spatial heterogeneity and extracellular polymeric substances may further modulate phage–host interactions [31,32].

Most evidence for phage-mediated biofilm control has been generated using laboratory-scale biofilm models, including static microtiter plate assays, stainless-steel coupons, or flow-cell systems, which enable controlled mechanistic evaluation of phage–biofilm interactions [33,34,35]. In contrast, biofilms formed on industrial seafood-processing surfaces are typically multispecies, structurally heterogeneous, and influenced by fluctuating temperature, nutrient availability, and sanitation regimes, which can reduce phage accessibility and efficacy compared with laboratory conditions [36,37].

Certain bacteriophages produce depolymerases or other enzymes capable of degrading extracellular polymeric substances, facilitating penetration of the biofilm matrix and enhancing bacterial inactivation under laboratory conditions [38,39,40]. However, the structural complexity and protective nature of industrial biofilms may limit enzyme diffusion and phage propagation, underscoring the need for validation under processing-relevant conditions. These properties nevertheless support the use of bacteriophages as complementary tools within sanitation and environmental monitoring programs rather than as stand-alone biofilm control measures.

Beyond planktonic bacteria, bacteriophages have demonstrated the capacity to reduce bacterial biofilms, which represent a persistent challenge in seafood processing environments. Biofilms formed by pathogens such as L. monocytogenes, Vibrio spp., Pseudomonas spp., and Shewanella spp. can adhere to equipment surfaces and exhibit enhanced tolerance to conventional sanitizers. Certain phages produce depolymerases or other enzymes capable of degrading extracellular polymeric substances, facilitating penetration of the biofilm matrix and enhancing bacterial inactivation [40,41]. These properties support the use of phages as complementary tools within sanitation and environmental monitoring programs.

While the fundamental steps of phage adsorption, genome injection, replication, and host cell lysis are well established, their efficiency in seafood systems is strongly influenced by environmental and physiological factors. Under refrigerated storage conditions commonly used for seafood, reduced temperatures can alter bacterial membrane fluidity and receptor expression, leading to slower adsorption kinetics and delayed initiation of the lytic cycle. In addition, bacterial metabolic activity is diminished under cold stress, which may limit phage replication rates despite successful adsorption [42,43,44].

Differences between Gram-positive and Gram-negative seafood pathogens further contribute to variability in phage efficacy. Gram-negative bacteria such as Vibrio spp. and Salmonella spp. possess outer membrane structures and lipopolysaccharides that can influence phage receptor accessibility, whereas Gram-positive organisms such as L. monocytogenes present thick peptidoglycan layers with distinct surface receptors. These structural differences affect both adsorption efficiency and susceptibility to phage-mediated lysis, particularly under food-relevant conditions [32,45,46].

Consequently, phage activity in seafood systems should not be assumed to be uniform across pathogens, matrices, or storage conditions, underscoring the importance of matrix-specific evaluation and temperature-appropriate formulation when translating phage mechanisms into practical biocontrol applications. Accordingly, under refrigerated conditions, phage-mediated bacterial reduction typically reflects delayed adsorption and slower intracellular replication cycles, resulting in cumulative lytic effects over extended storage periods rather than rapid lysis observed at optimal growth temperatures.

3.3. Advantages and Practical Implications Compared with Conventional Interventions

When evaluated against conventional antimicrobial interventions used in seafood processing, bacteriophages offer several distinct advantages, particularly in terms of specificity and compatibility with minimally processed products. Thermal treatments, chemical preservatives, and disinfectants are widely effective but can negatively affect sensory attributes, nutritional quality, and product yield, especially in raw and ready-to-eat seafood. In contrast, lytic bacteriophages have been reported to achieve pathogen reductions ranging from approximately 1 to 4 log CFU/g in seafood matrices during refrigerated storage, depending on phage formulation, target organism, and application timing, without measurable changes in texture, flavor, or appearance [7,8].

From a processing perspective, phages offer operational flexibility that distinguishes them from many conventional interventions. While heat-based treatments are limited to post-packaging or fully cooked products, and chemical sanitizers are often restricted to equipment or surface decontamination, phages can be applied at multiple points along the seafood production chain. These include aquaculture systems, post-harvest washing or icing, processing environments, active packaging, and refrigerated storage, enabling targeted intervention without requiring major process modifications [6]. Their activity at refrigeration temperatures is particularly relevant for seafood products that rely primarily on cold-chain control rather than thermal preservation.

Despite these advantages, bacteriophages do not universally outperform conventional antimicrobials and should not be viewed as direct replacements. Compared with broad-spectrum chemical preservatives or high-intensity physical treatments, phages generally exhibit slower inactivation kinetics and narrower antimicrobial spectra. Their effectiveness is highly dependent on the presence, physiological state, and accessibility of susceptible host bacteria, and reductions achieved by phage treatment alone may be lower than those obtained with aggressive chemical or thermal interventions under comparable conditions [24]. These constraints necessitate careful phage selection, dose optimization, and, in many cases, formulation of phage cocktails to ensure adequate pathogen coverage.

From a practical and regulatory standpoint, phage-based interventions align well with clean-label and sustainability-oriented processing frameworks, as they are naturally occurring biological entities and can reduce reliance on synthetic antimicrobials. However, their successful application requires integration into existing food safety management systems rather than stand-alone deployment. Reviews consistently emphasize that the greatest value of bacteriophages in seafood processing lies in their use as complementary tools within hurdle-based strategies and hazard analysis and critical control point (HACCP) programs, where they can enhance targeted pathogen control while minimizing quality losses associated with conventional interventions [6].

4. Target Pathogens and Spoilage Microorganisms in Seafood Systems Addressed by Bacteriophage Applications

4.1. Vibrio spp.

Species of Vibrio are among the most relevant bacterial hazards in seafood because they are indigenous to marine and estuarine environments, can be concentrated in filter-feeding shellfish, and may proliferate during temperature abuse. Clinically important species include V. parahaemolyticus and V. vulnificus, which are strongly associated with raw or undercooked seafood consumption, particularly oysters and other mollusks. Because Vibrio spp. contamination is primarily environmental in origin rather than solely facility-derived, post-harvest interventions that can be applied during cold-chain storage are particularly valuable for risk reduction in raw or minimally processed seafood products [47,48]. Conventional controls for Vibrio spp., such as refrigeration, icing, or depuration, are often insufficient because many Vibrio species remain viable at low temperatures and can persist on seafood surfaces without active growth. In addition, thermal treatments or chemical decontamination effective against Vibrio spp. are generally incompatible with raw seafood products due to quality and regulatory constraints, highlighting the need for targeted post-harvest interventions such as bacteriophage application.

Lytic Vibrio phages have been isolated from seafood matrices and surrounding waters, supporting the concept that phage–host interactions are already established within the seafood ecosystem [49,50,51]. Beyond in vitro reductions, several studies have explored phage utility in biologically relevant models and post-harvest contexts. For V. vulnificus, early evidence demonstrated that combining a V. vulnificus-specific phage with an oyster-derived antimicrobial factor reduced bacterial loads in oysters under chilled conditions, illustrating the potential for multi-hurdle biocontrol even in complex shellfish matrices [52].

In aquaculture-relevant contexts, phage strategies against V. parahaemolyticus have been explored not only as treatments but also as preventive measures, including feed-based delivery. For example, Ren et al. [53] reported protective effects against V. parahaemolyticus infection in sea cucumber using feed supplemented with freeze-dried phage preparations. In this study, the primary outcome was improved host survival and disease resistance rather than a quantitative assessment of Vibrio spp. load at harvest. Moreover, phage persistence on or within the host organism was not systematically evaluated at the time of harvest. As a result, while these findings support the potential of pre-harvest phage interventions to reduce infection pressure in aquaculture systems, their direct contribution to downstream food safety and pathogen reduction in products intended for consumption remains to be confirmed through targeted quantitative studies.

Collectively, these studies identify Vibrio spp. as a high-impact but technically challenging target for phage-based biocontrol along the seafood production chain. While phage interventions show promise, reported efficacy varies substantially across studies, reflecting strong dependence on seafood matrix characteristics, environmental conditions, and application timing. In practice, successful implementation requires careful, matrix-specific optimization, including consideration of salinity, surface properties, and storage temperature, as well as strategic deployment at stages where Vibrio spp. populations are most likely to persist or increase, such as post-harvest handling, depuration or relaying, and refrigerated storage [54,55,56]. These constraints underscore that phage-based control of Vibrio should be viewed as a complementary risk-reduction strategy rather than a universally effective intervention. Several studies have demonstrated significant reductions in Vibrio spp. in seafood matrices under refrigerated conditions following bacteriophage application, including reductions in V. parahaemolyticus in oysters, shrimp, and raw fish during chilled storage [18,19], as summarized in Table 2.

4.2. Listeria monocytogenes

L. monocytogenes remains a priority hazard for seafood processors because it can survive routine sanitation measures in processing environments, form biofilms on food-contact surfaces, and grow at refrigeration temperatures, features that make it especially problematic in ready-to-eat (RTE) seafood such as smoked fish, gravlax, and other lightly preserved products that do not undergo a final lethal processing step before consumption [36,57]. Unlike Vibrio, which is often environmentally introduced at harvest, L. monocytogenes is frequently linked to processing environments, equipment niches, and post-lethality contamination events, meaning contamination that occurs after a cooking or other validated lethal treatment [58,59].

Phage interventions for L. monocytogenes are among the most developed in food systems, with data supporting both direct application to food products and packaging- or film-based delivery approaches. A notable applied study showed that combining the bacteriocin enterocin AS-48 with the lytic phage P100 enhanced control of L. monocytogenes on fish products during refrigerated storage, illustrating a hurdle technology approach, in which multiple complementary preservation measures are applied together so that phages provide targeted specificity while additional antimicrobials reduce bacterial survival and regrowth [60].

Importantly for practical applications, there is also evidence for phage performance in more “real-world” seafood conditions, including smoked fish. Gündüz and Öztürk [61] evaluated Listex™ P100 applied directly to smoked fish and incorporated into an alginate-based edible film, demonstrating its effectiveness in controlling Listeria monocytogenes during refrigerated storage [61].

These findings collectively support the role of phages as practical tools for Listeria control in seafood, particularly where processors seek interventions that preserve product sensory quality and align with “clean-label” goals while strengthening post-lethality controls. Phage applications against L. monocytogenes in raw and ready-to-eat seafood products have resulted in multi-log reductions without adverse sensory effects (Table 2).

Listeria-specific bacteriophages have been reported to achieve reductions ranging from approximately 1 to 4 log CFU/g on raw and ready-to-eat seafood products during refrigerated storage, depending on phage formulation, application timing, and matrix characteristics [7].

4.3. Salmonella spp.

Although Salmonella spp. are most commonly associated with terrestrial foods, they remain a significant concern in seafood safety due to their ability to enter seafood supply chains through cross-contamination, contaminated water sources, ice, handling practices, and shared processing environments. Unlike Vibrio spp., which are indigenous to marine ecosystems, Salmonella spp. contamination in seafood is typically linked to anthropogenic factors, including poor hygiene, inadequate sanitation, or exposure to contaminated freshwater during harvesting, depuration, or processing [1]. These contamination pathways highlight the importance of targeted control measures within processing and handling environments, as effective interventions at these stages can substantially reduce the risk of Salmonella spp. introduction and persistence in seafood products.

Table 2. Verified examples of phage-based control of pathogens/spoilage organisms relevant to seafood systems.

Target Organism	Seafood/System Context	Intervention Format	Key Applied Outcome	Quantitative Outcome (Reported)	Reference
Vibrio vulnificus	Oysters	Phage + oyster extract antimicrobial factor	Reduced V. vulnificus load under chilled incubation	Approx. 1–2 log CFU/g reduction during refrigerated incubation	[52]
Vibrio parahaemolyticus	Sea cucumber (aquaculture)	Feed mixed with freeze-dried phage cocktail	Increased protection vs. infection; prevention-oriented approach	Improved host survival, bacterial load at harvest not quantified	[53]
Listeria monocytogenes	Raw/smoked fish	Bacteriocin (AS-48) + phage P100	Enhanced control during refrigerated storage	Approx. 2–3 log CFU/g greater reduction vs. single treatments	[60]
Listeria monocytogenes	Smoked rainbow trout	Direct phage + alginate film containing phage	Demonstrated effectiveness in smoked trout applications	Approx. 1–2 log CFU/g reduction over storage period	[61]
Salmonella Typhimurium	Raw salmon fillets and scallop adductors	Phage SLMP1	Reduced counts depending on dose/temp; storage-relevant	Up to 2–3 log CFU/g reduction, depending on conditions	[21]
Salmonella Typhimurium	Cockles (shellfish depuration)	Phage treatment during depuration	Reduced Salmonella load during purification process	Approx. 1 log CFU/g reduction during depuration	[62]
Vibrio cholerae	Seafood matrices (e.g., salmon/mussels)	Phage + HHP	Demonstrated synergy concept for nonthermal processing	Additional 1–2 log CFU/g reduction compared with HHP alone	[63]
Shewanella spp.	Chilled channel catfish	Virulent phage application	Biopreservation potential against chill spoilage	Shelf-life extension of 2–3 days under refrigeration	[22]

Table 2. Verified examples of phage-based control of pathogens/spoilage organisms relevant to seafood systems.

Target Organism	Seafood/System Context	Intervention Format	Key Applied Outcome	Quantitative Outcome (Reported)	Reference
Vibrio vulnificus	Oysters	Phage + oyster extract antimicrobial factor	Reduced V. vulnificus load under chilled incubation	Approx. 1–2 log CFU/g reduction during refrigerated incubation	[52]
Vibrio parahaemolyticus	Sea cucumber (aquaculture)	Feed mixed with freeze-dried phage cocktail	Increased protection vs. infection; prevention-oriented approach	Improved host survival, bacterial load at harvest not quantified	[53]
Listeria monocytogenes	Raw/smoked fish	Bacteriocin (AS-48) + phage P100	Enhanced control during refrigerated storage	Approx. 2–3 log CFU/g greater reduction vs. single treatments	[60]
Listeria monocytogenes	Smoked rainbow trout	Direct phage + alginate film containing phage	Demonstrated effectiveness in smoked trout applications	Approx. 1–2 log CFU/g reduction over storage period	[61]
Salmonella Typhimurium	Raw salmon fillets and scallop adductors	Phage SLMP1	Reduced counts depending on dose/temp; storage-relevant	Up to 2–3 log CFU/g reduction, depending on conditions	[21]
Salmonella Typhimurium	Cockles (shellfish depuration)	Phage treatment during depuration	Reduced Salmonella load during purification process	Approx. 1 log CFU/g reduction during depuration	[62]
Vibrio cholerae	Seafood matrices (e.g., salmon/mussels)	Phage + HHP	Demonstrated synergy concept for nonthermal processing	Additional 1–2 log CFU/g reduction compared with HHP alone	[63]
Shewanella spp.	Chilled channel catfish	Virulent phage application	Biopreservation potential against chill spoilage	Shelf-life extension of 2–3 days under refrigeration	[22]

Salmonella spp. has been detected in a wide range of seafood products, including raw fish fillets, shrimp, bivalve mollusks, and ready-to-eat seafood items. Shellfish are of particular concern because they can bioaccumulate enteric pathogens from contaminated waters through filter-feeding behavior, while post-harvest handling steps such as filleting, shucking, and packaging create additional opportunities for pathogen transfer. Several studies have demonstrated significant reductions in Salmonella spp. in seafood matrices under refrigerated conditions following bacteriophage application, primarily under laboratory-scale and pilot-scale experimental settings, highlighting their potential for targeted post-harvest control. For example, Xu et al. [21] reported that application of a lytic S. Typhimurium phage (SLMP1) reduced bacterial populations on raw salmon fillets and scallop adductors by approximately 2–3 log CFU/g during refrigerated storage at 4 °C, with reductions observed over several days. In that study, phage concentration was the primary determinant of efficacy, while storage temperature and initial bacterial load influenced the magnitude of reduction. Given that many seafood products are minimally processed and rely primarily on refrigeration for safety, targeted interventions that reduce Salmonella spp. loads without compromising product quality are highly desirable, particularly for products in which contamination can be concentrated through bioaccumulation mechanisms. Surveillance data further indicate that Salmonella spp. prevalence in seafood typically ranges from approximately 1–7%, depending on product type, region, and stage of processing, with higher detection rates often associated with raw or lightly processed products and post-harvest handling environments [64,65].

Bacteriophage-based strategies targeting Salmonella spp. have demonstrated promising results in seafood-relevant matrices. Xu et al. [21] reported that application of a lytic S. Typhimurium phage (SLMP1) significantly reduced bacterial populations on raw salmon fillets and scallop adductors, with efficacy influenced by phage concentration, storage temperature, and initial bacterial load. Importantly, phage treatment suppressed Salmonella spp. growth during refrigerated storage, indicating that phages can provide sustained control under cold-chain conditions typical of seafood distribution.

Beyond direct application to seafood products, phage interventions have been explored in process-integrated contexts, particularly shellfish depuration. Pereira et al. [62] demonstrated that incorporating bacteriophages into cockle depuration systems resulted in a significant reduction in S. Typhimurium levels, highlighting a unique opportunity to integrate phages into existing post-harvest purification processes. This approach is especially attractive because it leverages established infrastructure while enhancing pathogen removal efficiency without the use of chemical disinfectants.

From an applied perspective, the use of bacteriophages against Salmonella spp. in seafood systems offers several advantages. Phages can be deployed as processing aids through spraying, dipping, or incorporation into wash water and ice, enabling targeted control of incidental contamination events. Their specificity minimizes disruption to native microbiota and reduces the risk of sensory changes, which is particularly important for fresh and raw seafood products. Moreover, phages remain active at low temperatures, allowing continued suppression of Salmonella spp. during refrigerated storage.

However, effective application of phages against Salmonella spp. requires careful consideration of strain diversity and resistance development. Salmonella spp. exhibits substantial genetic and phenotypic heterogeneity, which can limit the efficacy of single-phage preparations. Consequently, phage cocktails with complementary host ranges are often necessary to achieve broad coverage and reduce the likelihood of resistant subpopulations. These considerations underscore the importance of pathogen surveillance, phage characterization, and formulation strategies tailored to specific seafood processing environments.

Overall, bacteriophage-based interventions represent a practical and flexible tool for mitigating Salmonella spp. risks in seafood systems, particularly when integrated into multi-hurdle safety strategies. Their greatest value lies in reinforcing hygiene controls, reducing cross-contamination during processing, and enhancing the effectiveness of post-harvest purification steps, rather than replacing fundamental sanitation and preventive measures.

4.4. Pathogenic Escherichia coli

Although pathogenic E. coli is less frequently associated with seafood than Vibrio spp. or L. monocytogenes, it remains a relevant hazard within seafood supply chains due to cross-contamination from water sources, handling practices, and shared processing environments. Pathogenic strains, including Shiga toxin–producing E. coli (STEC), may be introduced through contaminated ice, wash water, food-contact surfaces, or contact with other raw materials during processing and distribution. In such scenarios, E. coli contamination reflects failures in hygiene and environmental control rather than intrinsic seafood ecology, highlighting the need for targeted post-harvest interventions [66].

Bacteriophage-based approaches targeting pathogenic E. coli have been extensively explored in food systems, providing a strong conceptual and practical foundation for their application in seafood contexts. Lytic phage cocktails specific to E. coli O157:H7 and related STEC strains have demonstrated significant reductions on food surfaces and in food-contact environments without adversely affecting product quality [6,67]. While many of these studies were conducted in terrestrial food matrices, the underlying principles—surface decontamination, targeted pathogen reduction, and compatibility with cold storage—are directly applicable to seafood processing operations [68,69].

In seafood-relevant scenarios, phage treatments may be particularly useful as processing aids rather than primary interventions. For example, phage application to wash water, ice, or food-contact surfaces could reduce E. coli loads and limit cross-contamination during filleting, portioning, and packaging. Such uses align well with existing sanitation workflows and do not require substantial modification of processing infrastructure. Moreover, because phages are active at refrigeration temperatures, they may provide continued suppression of E. coli during chilled storage when bacterial growth is slow but still possible.

Synergistic strategies combining bacteriophages with non-thermal technologies have also been explored for enteric pathogens. Phage-assisted HHP treatment has been shown to enhance inactivation of E. coli and related enteric bacteria while allowing lower pressure levels to be used, thereby reducing potential quality degradation [63]. Although limited seafood-specific data are available, such combinations illustrate how phages can be integrated into hurdle-based preservation strategies, particularly for high-value seafood products where maintaining sensory quality is critical [62,70,71].

From an applied perspective, the use of bacteriophages against E. coli in seafood systems should be viewed as a risk-mitigation tool rather than a replacement for good hygiene practices, as reported biofilm reductions typically range from partial (1–3 log CFU/cm²) and are strongly surface- and strain-dependent under experimental conditions [72,73,74]. Their greatest value lies in the targeted control of incidental contamination events, reinforcement of sanitation measures, and reduction in pathogen transfer within processing environments. Continued research is needed to evaluate phage efficacy across diverse seafood matrices and to establish standardized application protocols tailored to seafood-specific processing conditions [75]. Accordingly, bacteriophage application should be positioned as one component of a multi-hurdle approach that integrates good hygiene practices, sanitation procedures, and complementary non-thermal interventions to enhance overall microbial risk mitigation.

4.5. Spoilage Bacteria (Shewanella spp. and Pseudomonas spp.) and Shelf-Life Extension

From an economic and sustainability perspective, spoilage control is as important as pathogen reduction in seafood systems. Psychrotrophic spoilage bacteria, particularly Shewanella spp. in chilled fish, contribute substantially to off-odors and quality deterioration during refrigerated storage.

In seafood systems, spoilage caused by Shewanella spp. and Pseudomonas spp. represents a major economic burden, often exceeding losses associated with pathogenic contamination. These organisms are responsible for the production of key spoilage metabolites, including trimethylamine (TMA) and total volatile basic nitrogen (TVB-N), which drive off-odors, discoloration, and rapid sensory rejection of seafood products. Several studies have demonstrated that targeted microbial control strategies can suppress the formation of these metabolites, thereby delaying spoilage onset and extending marketable shelf life. From an economic perspective, even modest reductions in spoilage-associated microbial activity can translate into significant reductions in product waste, improved cold-chain flexibility, and increased return on investment for processors, particularly for high-value fresh and minimally processed seafood products.

Compared with pathogen control, phage-based biopreservation of spoilage organisms is less mature but increasingly supported by targeted studies. Yang et al. [22] isolated virulent phages infecting Shewanella baltica and Shewanella putrefaciens and applied them to chilled channel catfish, demonstrating the feasibility of suppressing spoilage-associated bacterial growth and supporting shelf-life extension under cold storage conditions [22].

In contrast, phage control of Pseudomonas spp. spoilers in seafood remains an emerging and more fragmented area of research. For review purposes, Pseudomonas spp. are best presented as priority spoilage targets with a developing evidence base, while emphasizing that robust translation will require additional validation in real seafood matrices, such as fillets, modified atmosphere packaging systems, and fluctuating cold-chain conditions, as well as greater standardization of outcome reporting.

Representative effectiveness outcomes reported for bacteriophage applications targeting major seafood-associated bacteria are summarized in

Table 3. Reported effectiveness of bacteriophage applications against major seafood-associated pathogens.

Target Pathogen	Seafood Matrix	Phage Application Strategy	Storage/Condition	Reported Effectiveness	Reference
Listeria monocytogenes	Raw salmon, cold-smoked fish, ready-to-eat seafood	Surface spray or dip; single phage or phage cocktail	Refrigerated storage (≈4 °C)	~1–4 log CFU/g reduction, depending on formulation and matrix	[7,8]
Vibrio spp. (V. parahaemolyticus, V. vulnificus)	Shrimp, oysters, raw fish	Immersion or surface application; phage cocktails	Chilled storage	~2–5 log CFU/g reduction reported in laboratory and pilot-scale studies	[18,19]
Salmonella spp.	Fish fillets, seafood contact surfaces	Surface application or wash treatments	Refrigerated storage	~1–3 log CFU/g reduction, variable by strain and matrix	[21,22]
Spoilage bacteria (Pseudomonas, Shewanella spp.)	Various fresh seafood products	Surface application of spoilage-specific phages	Refrigerated storage	Delayed microbial growth and shelf-life extension of several days	[1]

.

5. Phage-Based Technologies in Seafood Processing and Storage

5.1. Phage Cocktails

One of the principal technological advances enabling practical bacteriophage application in seafood systems is the development of phage cocktails, which consist of two or more lytic phages combined to target a single pathogen or a group of closely related strains. This advance is particularly relevant to seafood systems, which are characterized by high microbial diversity, aquatic reservoirs, and frequent exposure to mixed pathogen populations compared with more uniform terrestrial food matrices. The primary rationale for using phage cocktails lies in overcoming the inherently narrow host range of individual phages. While host specificity is advantageous for targeted control, it can limit effectiveness in seafood environments, where pathogens often display substantial strain-level variability [6,9].

In seafood processing environments, pathogen heterogeneity commonly arises from multiple interacting sources, including raw materials, water, equipment surfaces, and personnel. Phage cocktails increase the likelihood that at least one phage in the formulation can infect and lyse a given bacterial strain, thereby providing broader host coverage and more consistent reductions, typically reported in the range of 1–3 log CFU across different seafood matrices. This approach has been particularly valuable for pathogens such as L. monocytogenes and V. parahaemolyticus, for which cocktail formulations have demonstrated greater and more reproducible reductions than single-phage applications under experimental processing conditions [1].

Beyond host-range expansion, phage cocktails also contribute to mitigating the development of phage resistance. Bacterial resistance can arise through receptor modification, restriction–modification systems, or CRISPR–Cas mechanisms. When multiple phages with distinct receptor targets and infection mechanisms are applied simultaneously, the probability that bacteria will develop resistance to all components of the cocktail is reduced, although resistance may still emerge under selective pressure [9,16]. In applied studies, this strategy has been associated with more sustained antimicrobial performance during refrigerated storage and repeated exposure cycles, primarily under laboratory and pilot-scale conditions.

From an operational perspective, phage rotation represents a feasible strategy for mitigating resistance development in seafood processing environments. Similar to disinfectant or antimicrobial rotation programs, phage formulations could be periodically adjusted based on environmental monitoring data, such as routine surface swabbing or molecular detection of dominant strains. Rotating or updating phage cocktails in response to shifts in microbial populations may help maintain efficacy over time and reduce selective pressure on any single phage component. While standardized rotation schedules have not yet been established, integration of phage rotation into existing hygiene monitoring programs offers a practical pathway for translating resistance management concepts into industrial practice.

5.2. Immobilized and Encapsulated Phage Systems

To address challenges related to phage stability, retention, and contact time in seafood systems, significant research has focused on immobilized and encapsulated phage technologies. These approaches involve incorporating phages into carrier matrices such as alginate, chitosan, gelatin, cellulose-based films, or other biopolymers that can be applied as coatings, edible films, or active packaging components [23,76]. Among these carriers, alginate-based systems are among the most extensively studied due to their high biocompatibility, mild gelation conditions, and superior ability to preserve phage infectivity compared with more rigid or chemically crosslinked polymer matrices.

Encapsulation within alginate beads or coatings has been shown to improve phage stability during refrigerated storage, with several studies reporting maintenance of infectivity over extended periods, often corresponding to reductions of ≤1 log PFU compared with rapid losses observed for free phages under similar conditions [61]. Similar protective effects have been reported for chitosan- and protein-based matrices, which may contribute additional antimicrobial activity either intrinsically, through their own antimicrobial properties, or synergistically by enhancing phage–bacterium contact at the food surface [23,77,78].

Immobilized phage systems also offer the advantage of controlled release, allowing phages to remain localized and active at food surfaces where contamination risk is highest. Release kinetics are typically evaluated using time-resolved diffusion or recovery assays, plaque-forming unit measurements, and surface-contact studies that quantify phage availability over storage time. In seafood products, where microbial growth is predominantly surface-associated, this localized delivery has been shown to enhance efficacy while reducing the total phage dose required. Phage-active packaging films have therefore been proposed as particularly suitable for chilled seafood, where prolonged surface contact during storage can suppress pathogen growth, as demonstrated in surface-inoculated fish and shellfish models [23,77,78,79]. While these systems have generally been reported to have minimal impact on appearance and sensory attributes, such effects are matrix-dependent and influenced by carrier composition and application conditions.

Despite these advantages, immobilization strategies must carefully balance phage protection with accessibility to bacterial hosts. Excessive encapsulation density, limited diffusion, or strong carrier–phage interactions may restrict phage–bacterium contact and reduce antimicrobial efficacy. Consequently, optimization of carrier composition, phage loading, and release kinetics remains a critical challenge and a key area of applied research for effective seafood-specific implementation of immobilized phage technologies.

5.3. Genetically Engineered and Modified Phages

Recent advances in molecular biology and synthetic biology have enabled the development of genetically engineered and modified bacteriophages with enhanced functionality, primarily aimed at overcoming limitations of naturally occurring phages in complex food systems, including seafood preservation and processing [16,76,79]. These efforts focus on improving phage performance, reliability, and predictability under food-relevant conditions rather than on immediate commercial deployment.

One major area of development involves engineering phages to expand host range through modification of receptor-binding proteins (RBPs), including tail fibers and baseplate structures. Such modifications can enable phages to recognize a broader spectrum of bacterial strains within a target species, addressing strain-level heterogeneity that is common in seafood matrices derived from open aquatic environments. Although host-range expansion strategies have shown promise in laboratory studies, their application in food systems remains largely experimental and requires further validation under realistic processing and storage conditions [79].

Another important advance concerns the incorporation or enhancement of phage-encoded enzymes, such as depolymerases and endolysins, which degrade extracellular polymeric substances and bacterial cell walls. These enzymes can improve phage access to bacteria embedded within biofilms on seafood surfaces and food-contact equipment, a persistent challenge in seafood safety management. In particular, depolymerase-producing phages have demonstrated enhanced antibiofilm activity against food-relevant pathogens, including L. monocytogenes and Vibrio spp., under controlled experimental conditions [79]. However, translation of these findings to industrial sanitation environments remains constrained by surface complexity and environmental variability.

Genetic modification has also been explored as a means to improve phage stability and functional performance under food-relevant stresses. Reported strategies include removal of undesirable genetic elements, optimization of lytic cycle regulation, and tailoring of phage genomes to reduce sensitivity to environmental factors such as pH fluctuations, ionic strength, and low-temperature storage. While these approaches provide a foundation for the development of next-generation phage formulations, most remain at the proof-of-concept stage and have not yet been implemented in commercial seafood applications [16,76].

Despite these technological advances, the use of genetically engineered phages in food systems is subject to additional regulatory and safety considerations compared with naturally occurring phages. Regulatory agencies generally require comprehensive genomic characterization and risk assessment to confirm the absence of virulence factors or antimicrobial resistance genes. Moreover, regulatory frameworks governing genetically modified organisms vary widely across jurisdictions, and consumer acceptance of engineered phages in food applications remains uncertain [1]. Consequently, most commercially available and near-term seafood applications continue to rely on naturally isolated or minimally modified lytic phages and phage cocktails.

Nevertheless, engineered phages represent a promising longer-term direction for addressing persistent contamination and biofilm-associated challenges that are difficult to control using conventional approaches alone. Their greatest potential lies within integrated preservation frameworks, where phages are combined with complementary antimicrobial hurdles to enhance microbial safety, stability, and shelf life in seafood systems (

Table 4. Summary of phage-based technological approaches for seafood processing and storage.

Phage-Based Technology	Primary Objective	Mechanism/Principle	Advantages for Seafood Applications	Key Limitations and Considerations	Representative Experimental Outcomes	Representative References
Phage cocktails	Broaden host range and enhance robustness	Combination of multiple lytic phages targeting different receptors or strains	Effective against heterogeneous pathogen populations; reduced resistance risk; adaptable to diverse seafood matrices	Requires careful phage selection and compatibility testing; increased formulation and regulatory complexity	~1–3 log CFU/g reductions in L. monocytogenes or Vibrio spp. on fish and shellfish during refrigerated storage (4–10 days), depending on cocktail composition	[6,9,16]
Immobilized phages (films/coatings)	Increase contact time at food surface	Phages embedded or bound to biopolymer matrices (alginate, chitosan, gelatin)	Improved stability during cold storage; localized antimicrobial activity; effective for surface contamination	Restricted diffusion; optimization of polymer composition and phage loading required	Sustained surface reductions (~1–2 log CFU/cm2) on smoked or raw fish surfaces during 7–21 days at refrigeration temperature	[23,61,76]
Encapsulated phages	Protect phages from environmental stress	Physical entrapment in microcapsules or gels	Enhanced tolerance to pH, salinity, and temperature fluctuations; prolonged phage viability	Potential delay in phage release; balance between protection and bioavailability required	Improved phage survival during storage and processing; delayed but prolonged antimicrobial activity under food-relevant pH and salinity	[76]
Phage-active packaging systems	Continuous antimicrobial action during storage	Incorporation of phages into packaging films or coatings	Sustained pathogen suppression during refrigerated storage; minimal impact on product sensory quality	Scale-up feasibility, cost, regulatory acceptance	Maintenance of pathogen suppression throughout chilled storage (up to 14–21 days), primarily demonstrated at laboratory and pilot scale	[23,78]
Genetically engineered phages	Enhance functionality (host range, antibiofilm activity)	Modification of receptor-binding proteins or addition of enzymatic functions	Potential to overcome limitations of natural phages; improved control of persistent contamination	Regulatory uncertainty; consumer perception; limited food-specific approvals	Demonstrated host-range expansion and antibiofilm activity in laboratory models; food-system validation remains limited	[16,79]

).

6. Integration of Bacteriophages with Other Preservation Strategies

The complexity of seafood matrices and the diversity of contamination routes make it unlikely that a single preservation strategy can provide robust and consistent microbial control across all products and processing conditions. Consequently, modern seafood safety increasingly relies on hurdle technology, in which multiple interventions are combined to achieve enhanced microbial inactivation while minimizing adverse effects on quality. Within this framework, bacteriophages are particularly well suited for integration with other preservation strategies because of their specificity, biological compatibility, and activity under refrigerated conditions. Rather than functioning as stand-alone interventions, phages can complement chemical, physical, and packaging-based approaches to achieve synergistic and more resilient control of seafood-associated pathogens (Figure 1).

6.1. Phages Combined with Natural Antimicrobials

6.1.1. Organic Acids

Organic acids such as lactic, acetic, and citric acids are widely used in seafood processing as surface decontaminants due to their broad antimicrobial activity, regulatory acceptance, and low cost [80,81]. However, their effectiveness can be limited by the buffering capacity of seafood matrices and by sensory constraints when applied at higher concentrations, which may adversely affect flavor, odor, or texture [82,83]. Combining organic acids with bacteriophages has therefore emerged as a promising strategy to enhance antimicrobial efficacy while allowing reduced acid concentrations. Studies have shown that organic acids can increase bacterial membrane permeability or induce sublethal stress, thereby facilitating phage adsorption and infection, resulting in greater reductions than either intervention alone [67,84].

Several studies have demonstrated that organic acids can increase bacterial susceptibility to phage infection by altering cell surface properties or weakening membrane integrity. For example, Zheng et al. [85] showed that the combined application of lytic phages and citric acid resulted in a greater reduction in V. parahaemolyticus in seafood systems than either treatment alone, suggesting a synergistic interaction. Similarly, experimental evidence indicates that combining bacteriophages with mild organic acid treatments can enhance the inactivation of E. coli O157:H7 on food matrices during refrigerated storage compared to phage application alone. Acid-induced sublethal stress is thought to facilitate phage adsorption and intracellular replication by compromising bacterial cell envelope integrity and membrane-associated defense mechanisms [16,35,86].

From an applied perspective, phage–organic acid combinations are particularly attractive for post-harvest seafood treatments, such as surface sprays, dips, or ice slurries, where short contact times and mild conditions are required to preserve sensory quality. These combinations align well with clean-label strategies, as both components are naturally derived.

6.1.2. Bacteriocins

Bacteriocins are ribosomally synthesized antimicrobial peptides produced by bacteria, with nisin and enterocins being among the most studied for food applications. While bacteriocins exhibit strong activity against Gram-positive pathogens such as L. monocytogenes, their spectrum is narrow and may not prevent regrowth when used alone [87,88].

Combining bacteriocins with bacteriophages offers complementary modes of action: bacteriocins disrupt bacterial membranes or metabolic processes, while phages induce targeted lysis. Baños et al. [60] demonstrated that the combined use of enterocin AS-48 and a Listeria-specific phage (P100) resulted in enhanced control of L. monocytogenes on fish products during refrigerated storage compared with individual treatments. More recently, Soni and Nannapaneni [89] showed that nisin and phage ListShield acted synergistically to eliminate L. monocytogenes biofilms on smoked salmon surfaces, with the combination being more effective than sequential treatments [89,90,91].

For seafood processors, phage–bacteriocin combinations offer a biologically rational approach to strengthening control of persistent pathogens, particularly in ready-to-eat products. These combinations may also reduce the selective pressure for resistance development associated with single antimicrobials.

6.1.3. Plant-Derived Compounds

Essential oils (EOs) and their bioactive components (e.g., carvacrol, thymol, eugenol) are gaining attention for seafood preservation due to their antioxidant and antimicrobial properties [92,93]. However, their strong aroma and potential for lipid oxidation limit direct application. Phages can be combined with sub-inhibitory concentrations of EOs to achieve enhanced microbial killing without compromising sensory attributes [94,95].

Plant-derived compounds such as essential oil components have been shown to increase bacterial membrane permeability, which can enhance bacteriophage adsorption and infection efficiency. Sub-inhibitory concentrations of compounds such as thymol have been reported to potentiate phage activity against Gram-negative spoilage bacteria by promoting receptor accessibility. In addition, biopolymers such as chitosan have been explored as carriers for bacteriophages, providing both protective and antimicrobial functions and contributing to improved control of Vibrio spp. in seafood-related systems [6,76].

6.1.4. Synergistic Effects and Practical Implications

The complexity of seafood matrices and the diversity of contamination routes make it unlikely that a single preservation strategy can provide robust and consistent microbial control across all products and processing conditions. Consequently, modern seafood safety increasingly relies on hurdle technology, in which multiple interventions are combined to achieve enhanced microbial inactivation while minimizing adverse effects on quality [96]. Within this framework, bacteriophages are particularly well suited for integration with other preservation strategies because of their specificity, biological compatibility, and activity under refrigerated conditions [6].

Among available hurdles, the most consistently reported synergies with bacteriophages involve natural antimicrobials such as organic acids and bacteriocins [60,90], non-thermal physical treatments that induce sublethal bacterial injury, including high hydrostatic pressure and pulsed electric fields [63,97,98], and surface-focused interventions such as antimicrobial coatings and phage-active packaging systems [23,61]. These complementary hurdles can enhance phage adsorption, improve access to stressed or biofilm-embedded cells, and reduce post-treatment regrowth during cold storage. Rather than functioning as stand-alone interventions, bacteriophages therefore complement chemical, physical, and packaging-based approaches to achieve more resilient and food-compatible control of seafood-associated pathogens [6].

The success of phage–natural antimicrobial combinations depends on careful optimization of treatment sequence, concentration, and environmental conditions. Pre-treatment with an antimicrobial may increase bacterial susceptibility to phage infection, whereas simultaneous application can result in cooperative antimicrobial effects. However, antagonistic interactions may occur if certain antimicrobials inactivate phages or induce rapid bacterial lysis before productive phage replication can occur (

Table 5. Examples of bacteriophage synergy with natural antimicrobials in seafood systems.

Combination	Target Pathogen/Spoiler	Seafood Matrix	Key Outcome	Reference
Phage cocktail + Citric acid	Vibrio parahaemolyticus	Shrimp, Oysters	Synergistic reduction; >4-log CFU/g reduction vs. <2-log by single treatments	[85]
Phage P100 + Enterocin AS-48	Listeria monocytogenes	Cold-smoked salmon, trout	Enhanced control during storage; delayed regrowth for >21 days at 4 °C	[60]
Phage + Thymol	Listeria monocytogenes	Model food systems	Enhanced bacterial reduction compared to single treatments	[35]
Phage cocktail + Chitosan coating	Vibrio harveyi	Shrimp	Synergistic reduction in biofilms; improved preservative effect during chilled storage	[99]
Phage ListShield + Nisin	Listeria monocytogenes (biofilm)	Smoked salmon surfaces	Complete biofilm eradication; synergistic effect observed	[100,101]

).

Overall, integrating bacteriophages with natural antimicrobials represents a relatively low-barrier and high-impact strategy for improving seafood safety, particularly in minimally processed products where mild, quality-preserving interventions are preferred.

6.2. Phages and Non-Thermal Technologies

6.2.1. High Hydrostatic Pressure (HHP)

High hydrostatic pressure is an established non-thermal technology used in seafood processing to inactivate microorganisms while preserving sensory quality. However, high pressure levels may affect texture or increase costs. Combining HHP with bacteriophages offers a means to reduce pressure intensity while maintaining safety.

Ahmadi et al. [63] demonstrated that phage-assisted HHP treatment enhanced inactivation of V. cholerae in seafood matrices, allowing effective control at lower pressure levels. The proposed mechanism involves pressure-induced sublethal injury that increases bacterial susceptibility to phage infection. Supporting this concept, previous studies have shown that bacteriophages can effectively infect and lyse pressure-injured bacterial cells following HHP treatment, resulting in enhanced microbial inactivation compared with pressure treatment alone. Sublethal pressure is thought to increase cell envelope permeability and reduce bacterial defense mechanisms, thereby facilitating subsequent phage adsorption and replication [63].

6.2.2. Cold Plasma

Cold plasma technology generates reactive oxygen and nitrogen species (RONS) capable of inactivating microorganisms at low temperatures. Integrating phages with cold plasma has been proposed as a complementary strategy, where plasma reduces surface contamination and phages provide targeted follow-up control.

Cold plasma treatment generates reactive oxygen and nitrogen species that can induce sublethal damage to bacterial cell membranes and disrupt biofilm structures. These plasma-induced effects have been shown to increase bacterial susceptibility to antimicrobial agents by compromising cell envelope integrity and surface-associated defense mechanisms. Although direct experimental studies combining cold plasma and bacteriophages in seafood systems remain limited, the mechanistic basis for potential synergy is well supported. Sublethal membrane damage and biofilm disruption caused by plasma exposure are expected to enhance bacteriophage adsorption and access to bacterial receptors, thereby facilitating subsequent phage infection and lytic activity [16,102].

6.2.3. Pulsed Electric Fields and Ultrasound

Pulsed electric fields induce transient pore formation in microbial cell membranes. Although most phage–PEF studies have focused on liquid foods, the principles are applicable to seafood brines or wash waters. PEF treatment induces transient pore formation in bacterial cell membranes, leading to sublethal injury under mild processing conditions. Such membrane permeabilization has been shown to increase bacterial susceptibility to antimicrobial agents by compromising barrier functions and stress response systems. Although direct experimental studies combining PEF and bacteriophages in seafood matrices remain limited, the mechanistic basis for potential synergy is well supported. PEF-induced membrane damage is expected to enhance bacteriophage adsorption and facilitate genome injection, thereby improving subsequent phage-mediated inactivation of stressed bacterial cells [4,16,103].

Similarly, ultrasound treatment has been shown to disrupt microbial cell walls and biofilm structures through cavitation-induced shear forces and localized pressure gradients. These effects can increase the susceptibility of bacteria to antimicrobial agents by improving access to embedded or surface-associated cells. Although direct experimental studies combining ultrasound and bacteriophages in seafood matrices remain limited, the mechanistic basis for potential synergy is well supported. Ultrasound-induced biofilm disruption and membrane perturbation are expected to facilitate bacteriophage penetration and adsorption, thereby enhancing phage-mediated inactivation of spoilage bacteria [16,86,104].

6.3. Phage-Active Packaging Systems

6.3.1. Active and Intelligent Packaging

Active packaging systems incorporate antimicrobial agents directly into packaging materials to inhibit microbial growth during storage and distribution. Bacteriophages are particularly attractive for such systems due to their host specificity, stability under refrigerated conditions commonly used for seafood and ready-to-eat products, and generally minimal impact on sensory attributes when applied at appropriate doses and within compatible carrier matrices. Accordingly, phage-based active packaging has been discussed primarily within the framework of biopolymer films and coatings. These systems mainly rely on polysaccharide-based materials, such as alginate, chitosan, and cellulose derivatives, as well as protein-based matrices, as summarized in recent authoritative reviews [23,77,78].

Experimental evidence supporting phage incorporation into packaging-relevant matrices has begun to emerge. Notably, Martínez-Soto et al. [105] demonstrated that bacteriophages can be successfully incorporated into electrospun polymer nonwoven materials, retaining infectivity and achieving approximately 1–2 log CFU reductions in S. Enteritidis on food-contact surfaces over short-term storage, thereby confirming both antimicrobial activity and functional stability within the packaging matrix.

Although this study was conducted in poultry systems and targeted Salmonella spp. rather than L. monocytogenes, it provides direct evidence for the feasibility of embedding viable bacteriophages into fibrous packaging structures using electrospinning. This study is frequently cited as an early experimental demonstration of phage-loaded nanofibrous packaging systems.

With respect to L. monocytogenes, the current literature supports the use of bacteriophages as biocontrol agents in food systems, including seafood; however, applications to date have primarily involved direct surface treatments or incorporation into coatings rather than fully developed intelligent packaging systems [84,106]. Comprehensive reviews indicate that immobilization or encapsulation of phages within packaging matrices can enhance stability and localize antimicrobial activity at the food–package interface. Nevertheless, challenges remain related to controlled release, diffusion through food surfaces, and regulatory requirements, including migration limits, material compatibility, and approval pathways for active packaging components [23,41,107].

At present, intelligent packaging concepts that combine bacteriophages with sensors, pH indicators, or time–temperature integrators remain largely theoretical. Although reviews describe the potential integration of phages into responsive packaging systems capable of releasing phages in response to spoilage-related environmental changes, peer-reviewed studies demonstrating fully functional, phage-triggered intelligent packaging under real food storage conditions are currently lacking. Accordingly, intelligent phage-based packaging should be regarded as an emerging research direction rather than an established technology [78,108]. This limitation reflects several unresolved technical challenges, including maintaining phage viability during integration with sensing elements, designing reliable trigger mechanisms for on-demand phage release, and preventing premature activation in response to non-microbial environmental fluctuations. In addition, achieving synchronized performance between sensing, signal processing, and antimicrobial release within a single packaging system remains a significant engineering challenge.

6.3.2. Shelf-Life Extension and Cold-Chain Compatibility

Phage-active packaging systems are particularly advantageous for seafood because microbial growth is often concentrated at product surfaces during refrigerated storage. Sustained phage release can suppress pathogen growth over extended periods without altering sensory attributes. Studies have demonstrated reduced Listeria spp. contamination and delayed spoilage in phage-coated or phage-embedded packaging systems under cold storage.

From a cold-chain perspective, phages retain activity at low temperatures and do not require activation by heat or moisture, making them compatible with existing seafood storage and distribution practices. However, challenges related to large-scale manufacturing, regulatory approval, and cost-effectiveness must be addressed before widespread adoption. Ongoing research focuses on improving phage stability in polymers during packaging extrusion and storage [76].

7. Challenges and Limitations in Industrial Application

7.1. Host Specificity as a Practical Constraint

The narrow host specificity of bacteriophages, while advantageous for targeted pathogen control, also represents a practical limitation for their application in seafood preservation. Seafood products and processing environments are often contaminated with diverse and heterogeneous bacterial populations, including multiple species and strain variants of both pathogenic and spoilage microorganisms. In such complex microbial ecosystems, a single phage preparation may fail to inactivate all relevant target strains, potentially resulting in incomplete microbial control. This limitation is particularly relevant for seafood matrices sourced from open aquatic environments, where microbial diversity and strain variability are high.

To address this constraint, several mitigation strategies have been proposed, including the use of phage cocktails with complementary host ranges, periodic rotation or updating of phage formulations to match circulating strains, and integration of phages with non-specific preservation hurdles such as organic acids, non-thermal processing technologies, or antimicrobial packaging. These combined approaches can broaden antimicrobial coverage while retaining the selectivity and ecological advantages of phage-based interventions. Nonetheless, the need for careful phage selection and formulation underscores the importance of strain surveillance and product-specific validation prior to industrial implementation.

7.2. Phage Resistance Development

One of the most frequently cited challenges in the industrial application of bacteriophages is the development of bacterial resistance. Resistance mechanisms primarily involve modifications or loss of bacterial surface receptors required for phage adsorption, including alterations in cell wall teichoic acids, membrane proteins, or surface polysaccharides. In addition, bacteria may employ restriction–modification systems, CRISPR–Cas immunity, or abortive infection mechanisms, all of which can limit successful phage replication [109,110].

From an industrial perspective, resistance does not necessarily lead to immediate failure of phage interventions but can reduce antimicrobial efficacy over time, particularly when single phages or static formulations are used repeatedly within the same processing environment. Reviews focusing on food applications consistently emphasize that phage resistance is most likely to emerge when phages are treated as stand-alone interventions rather than components of an integrated food safety strategy [10,111].

To mitigate resistance development, several strategies have been proposed. Phage cocktails, composed of multiple phages targeting different bacterial receptors, significantly reduce the likelihood of resistance arising through a single mutational pathway [112]. Phage rotation, analogous to antimicrobial stewardship programs, has also been suggested for facilities with persistent resident strains [10]. Additionally, combining phages with other hurdles such as sanitation, refrigeration, or mild physical treatments can reduce bacterial population sizes and slow resistance selection [111].

7.3. Stability Under Processing and Storage Conditions

Temperature stability is a critical factor for industrial deployment. Although bacteriophages are generally compatible with refrigerated conditions used for seafood storage, stability varies substantially among phages and formulations. Some phages retain infectivity for extended periods at low temperatures, while others exhibit gradual titer loss depending on buffer composition and food matrix interactions [113,114,115].

pH and ionic conditions also influence phage viability. Deviations from optimal pH ranges can destabilize capsid proteins, while high salt concentrations or divalent ions may promote aggregation or inactivation. This is particularly relevant for seafood products, which often involve brining, marination, or acidic processing steps [12].

The seafood matrix itself presents additional challenges. Proteins and lipids may adsorb or entrap phage particles, while complex surface structures and biofilms can shield target bacteria from phage contact. Moreover, background microbiota may indirectly affect phage activity by altering local microenvironments without serving as hosts [1]. Consequently, phage performance is highly product-specific, and results obtained in one seafood matrix may not be directly transferable to another.

To address these issues, recent research emphasizes the importance of formulation and delivery systems, including stabilizing solutions, encapsulation, and immobilization within carrier matrices, to preserve phage infectivity and prolong functional shelf life.

7.4. Regulatory Frameworks and Approval Pathways

Regulatory approval remains a significant barrier to the widespread industrial adoption of phage-based interventions. In the United States, several bacteriophage preparations have been cleared through the Generally Recognized as Safe (GRAS) pathway, most notably the anti-L. monocytogenes phage preparation P100 [116]. However, regulatory oversight varies according to product classification, intended use, and food category, often requiring coordination among multiple regulatory authorities [14].

In the European Union, the European Food Safety Authority (EFSA) has evaluated bacteriophages within the context of food production and issued scientific opinions on their safety and mode of action, including formal assessments of Listex™ P100 [2,116]. Nevertheless, bacteriophages are not uniformly classified across EU member states, and uncertainty remains regarding whether they should be regulated as processing aids, food additives, or decontamination agents, resulting in case-specific approval pathways.

Beyond the United States and the European Union, regulatory heterogeneity poses a major challenge for multinational seafood producers. In China and other Asian markets, regulatory frameworks for bacteriophage-based interventions remain less standardized, with approval processes evolving alongside broader food biotechnology regulations. Differences in data requirements, labeling rules, and approval timelines across jurisdictions can significantly delay commercialization, even when scientific evidence supports safety and efficacy [10,14]. Collectively, these jurisdictional differences influence labeling obligations, market access, and the scalability of phage-based interventions for globally distributed seafood products.

7.5. Consumer Acceptance and Perception

Beyond technical and regulatory hurdles, consumer perception plays a decisive role in the success of phage-based technologies. The term “virus” often carries negative connotations, and public awareness of bacteriophages remains limited, contributing to initial consumer skepticism toward their use in foods [117,118,119,120]. Survey-based studies indicate that acceptance is initially low but improves significantly when consumers are informed that phages are naturally occurring and selectively target harmful bacteria without affecting humans [13,15].

Studies examining willingness to purchase phage-treated foods suggest that acceptance increases when phages are framed as food safety tools rather than as additives, particularly when linked to the prevention of serious foodborne illnesses such as listeriosis [15]. However, acceptance varies by product type, cultural context, and trust in regulatory oversight.

Consequently, effective communication and clean-label positioning are essential. Reviews emphasize the importance of transparent messaging that explains what bacteriophages are, how they function, and why they are used, while avoiding technical jargon that may reinforce consumer concerns [10,111].

8. Practical Considerations for Implementation in the Seafood Industry

Translating scientific research into robust, day-to-day industrial practice is a critical step for improving seafood safety and quality. While laboratory-scale studies provide essential mechanistic insight, their real value lies in practical applicability within existing processing, regulatory, and economic constraints. Accordingly, this section outlines key considerations for implementing emerging methodologies, such as rapid monitoring tools, predictive models, and targeted interventions, within seafood operations, supporting the assessment-to-action pathway illustrated in Figure 2.

8.1. Integration with HACCP Frameworks

HACCP system remains the globally recognized foundation of seafood safety management. Any new intervention or monitoring technology must be compatible with HACCP principles to ensure regulatory compliance and operational feasibility. Rather than replacing traditional HACCP elements, emerging tools are best positioned as enhancements to hazard analysis, monitoring, verification, or corrective action.

Rapid detection methods for pathogens or spoilage organisms can strengthen monitoring at Critical Control Points (CCPs) by providing timely, process-relevant data rather than retrospective end-product results [121]. In addition, outputs from quantitative risk assessment or predictive microbiology models can be used to refine critical limits or justify process deviations based on scientific evidence. This allows HACCP plans to evolve from static compliance documents into adaptive, data-driven management systems grounded in risk-based decision-making.

8.2. Application Points Across the Seafood Supply Chain (Harvest → Storage)

Effective implementation depends on identifying intervention points where technologies provide the greatest preventive value.

At Harvest and Onboard Vessels: Rapid at-sea quality assessment tools, such as handheld sensors for histamine or freshness indicators based on volatile compounds, enable early segregation of high-risk catch. This supports real-time decisions related to icing, storage duration, or product destination, reducing the likelihood of downstream spoilage or safety failures [122].

During Processing: Within processing facilities, automated or continuous monitoring systems can detect contamination or early spoilage before irreversible quality loss occurs. Multisensor or spectroscopic sorting technologies allow non-destructive screening of raw materials, while environmental monitoring of surfaces and processing environments supports proactive contamination control. Early detection at this stage is particularly valuable, as interventions become increasingly limited once products are portioned or packaged [123].

Storage and Transportation: Cold-chain management remains a dominant determinant of seafood shelf life and safety. Time–temperature integrators (TTIs) and sensor-based data loggers provide objective evidence that temperature conditions assumed in shelf-life models are maintained in practice. These tools also enhance traceability and accountability across supply chain partners, supporting quality assurance at receipt and distribution stages [124].

8.3. Compatibility with Existing Sanitation Programs

New interventions must complement, rather than complicate, established sanitation standard operating procedures. Biologically based approaches, such as bacteriophages or biofilm-targeting enzymes, should be evaluated for compatibility with conventional chemical sanitizers, contact times, and cleaning schedules. In most cases, these approaches are most effective when applied as targeted or supplemental treatments, particularly in persistent contamination niches.

Verification of sanitation efficacy can also be strengthened through advanced surface monitoring approaches. Rapid hygiene indicators, when used alongside targeted microbiological tests, provide more timely and actionable feedback than traditional plating methods alone. Importantly, any added monitoring step must fit within existing operational workflows to ensure sustained adoption [125,126].

8.4. Cost, Scalability, and Return on Investment

Economic feasibility ultimately determines whether scientific advances transition into routine practice. Cost considerations extend beyond initial equipment purchase and include consumables, maintenance, data management, and personnel training. Technologies that are modular, portable, and readily integrated into existing processing lines tend to offer greater scalability across processors of different sizes [127,128].

Return on investment (ROI) should be evaluated holistically. Reduced product loss, fewer recalls, improved shelf-life predictability, and enhanced market access represent tangible benefits that can offset implementation costs. Demonstrating these benefits through pilot-scale validation or economic modeling provides a compelling rationale for adoption and supports informed decision-making by industry stakeholders [127]. By targeting dominant spoilage bacteria and suppressing the formation of key spoilage metabolites such as trimethylamine and total volatile basic nitrogen, phage-based interventions have the potential to reduce product rejection rates and economic losses, complementing their role in pathogen control.

8.5. From Assessment to Action

Successful implementation requires viewing new tools not as standalone solutions, but as components of a broader food safety ecosystem. By embedding them within HACCP plans, applying them strategically along the supply chain, ensuring compatibility with sanitation programs, and rigorously evaluating cost-effectiveness, the seafood industry can translate scientific assessment into practical action.

9. Future Perspectives and Research Needs

Despite significant advances in the application of emerging biocontrol, monitoring, and predictive tools for seafood safety, several critical research gaps must be addressed before widespread and sustained industrial adoption can be achieved. Future efforts should prioritize standardization, long-term performance evaluation, large-scale validation, and regulatory alignment to ensure that scientific innovation translates into reliable, globally applicable practice.

9.1. Standardization of Application Protocols

One of the primary barriers to broader adoption of novel interventions—particularly biologically based approaches such as bacteriophages or enzymatic treatments—is the lack of standardized application protocols. Variability in dose, contact time, application method, and environmental conditions complicates comparisons across studies and limits reproducibility under commercial conditions [35].

Future research should focus on defining matrix-specific and process-specific protocols, accounting for factors such as seafood species, surface characteristics, temperature, and organic load. Establishing standardized performance metrics and reporting frameworks will be essential to support regulatory evaluation, facilitate technology transfer, and enable meaningful meta-analyses across studies [111,129].

9.2. Long-Term Resistance Monitoring

The potential for microbial adaptation or resistance development remains a key concern for any targeted antimicrobial strategy. Although bacteriophages exhibit a fundamentally different mode of action compared with chemical antimicrobials, bacterial resistance to phages has been documented under laboratory and applied conditions [130].

Long-term surveillance studies are therefore needed to evaluate resistance dynamics in real processing environments, where selective pressures differ markedly from controlled laboratory systems. Research should emphasize rotational strategies, phage cocktails, and integration with conventional sanitation programs to mitigate resistance risks. Importantly, resistance monitoring should be incorporated into routine environmental and product testing frameworks to ensure early detection and adaptive management [108,130].

9.3. Large-Scale Industrial Trials

While proof-of-concept and pilot-scale studies provide essential feasibility data, the transition to commercial implementation requires validation under full-scale industrial conditions. Large-scale trials are needed to assess robustness, consistency, and operational feasibility across diverse processing environments, product types, and seasonal variability [131,132].

Such trials should evaluate not only microbial reduction efficacy, but also impacts on product quality, shelf life, workflow efficiency, and cost-effectiveness. Collaboration between academia, industry, and regulatory agencies will be critical to designing trials that generate data suitable for both operational decision-making and regulatory submission [133].

9.4. Regulatory Harmonization and Global Alignment

Regulatory heterogeneity across jurisdictions remains a significant challenge for technologies intended for global seafood markets. Differences in approval pathways, data requirements, and risk assessment frameworks can delay adoption and limit international trade. While some regions have established mechanisms for approving novel interventions, others rely on case-by-case evaluations, increasing uncertainty for industry stakeholders [134,135].

Future research should support science-based regulatory harmonization, including the development of shared risk assessment methodologies and guidance documents. Generating transparent, high-quality safety and efficacy data will be essential for building regulatory confidence and facilitating mutual recognition across markets. Alignment between regulatory expectations and industrial realities will ultimately determine the pace at which innovation is integrated into global seafood safety systems [121,136].

10. Conclusions

Current evidence demonstrates that bacteriophages represent a practical and scientifically sound biocontrol strategy for improving seafood safety and quality across processing and storage environments. Their high host specificity, activity at refrigeration temperatures, and compatibility with minimally processed foods position phages as valuable tools for targeting key seafood-associated pathogens and spoilage organisms without compromising sensory or nutritional attributes. When applied strategically, phage-based interventions can reinforce existing food safety systems by reducing pathogen loads, mitigating post-process contamination, and supporting shelf-life extension in chilled seafood products.

From an applied perspective, the greatest value of bacteriophage technology lies in its integration within established seafood safety frameworks rather than its use as a standalone intervention. Phages can be incorporated into HACCP-based programs, sanitation strategies, and hurdle technology approaches to provide targeted control at critical points along the seafood supply chain. Advances in phage formulation, including cocktails, immobilized systems, and active packaging applications, further enhance their robustness and adaptability under real processing and storage conditions, addressing many of the practical limitations historically associated with biological interventions.

Importantly, bacteriophage-based approaches align closely with sustainability goals and clean-label trends that increasingly shape seafood markets. As naturally occurring biological entities, phages offer an alternative to broad-spectrum chemical preservatives and intensive physical treatments, enabling more selective microbial control while reducing chemical inputs, product waste, and environmental impact. Their use supports transparent, science-based food safety strategies that resonate with consumer demand for minimally processed foods and environmentally responsible production practices.

In conclusion, bacteriophages should be viewed as enabling components of a modern seafood safety ecosystem that bridges scientific innovation and industrial application. Continued progress will depend on standardized application protocols, long-term performance monitoring, large-scale validation, and regulatory alignment. By addressing these needs and embedding phage technologies within holistic food safety management systems, the seafood industry can enhance microbial control, support sustainability objectives, and meet evolving regulatory and consumer expectations in a robust and defensible manner.