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Review

Bacteriophages as a Sustainable Tool for Plant Disease Management: Benefits and Challenges

by
Anna Hoffmann
1,
Katarzyna Sadowska
2,
Weronika Zenelt
2 and
Krzysztof Krawczyk
1,*
1
Virology and Bacteriology Department, Institute of Plant Protection—National Research Institute, 60-318 Poznań, Poland
2
Plant Disease Clinic and Bank of Plant Pathogen, Institute of Plant Protection—National Research Institute, 60-318 Poznań, Poland
*
Author to whom correspondence should be addressed.
Agronomy 2025, 15(11), 2507; https://doi.org/10.3390/agronomy15112507
Submission received: 24 September 2025 / Revised: 20 October 2025 / Accepted: 27 October 2025 / Published: 28 October 2025
(This article belongs to the Special Issue Post-harvest Pest and Disease Management—2nd Edition)
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Abstract

Bacterial diseases cause significant economic losses and pose a major challenge to global crop yields. These diseases reduce yields and affect food security, particularly for small-scale farmers in developing regions. Post-harvest losses also contribute to resource waste, soil degradation, and deforestation. Conventional management strategies, such as synthetic fungicides and antimicrobials, raise concerns about environmental sustainability, human health, and pathogen resistance. Bacteriophages—viruses that selectively infect bacterial pathogens—offer a highly specific and eco-friendly alternative for disease management both post-harvest and pre-harvest, reducing the need for chemical pesticides throughout the plant lifecycle. This review examines bacteriophage biology, advantages over traditional treatments, and challenges to their application. Phages effectively target pathogens such as Pectobacterium, Xanthomonas, Xylella, Clavibacter, and Dickeya, while preserving beneficial microorganisms. Key challenges include bacterial resistance, regulatory hurdles, and phage stability under environmental conditions. Advances in phage genomics, bioengineering, and formulation have enhanced viability and efficacy, supporting phages as promising biocontrol agents. Integrating phage therapy with other eco-friendly strategies may improve effectiveness further. Future research should focus on optimizing production, refining regulations, and large-scale field studies to ensure practical feasibility. Addressing these issues will help bacteriophages contribute significantly to sustainable plant disease management and global food security.

1. Introduction: The Need for Sustainable Plant Disease Management

Agricultural products can generally be classified into two categories: durables and perishables. While durable crops like cereals and grains can be stored for years under proper conditions, perishable products such as fruits and vegetables require bacterial disease management to maintain their quality. One of the major challenges in modern agriculture is minimizing storage diseases, which cause significant economic and social consequences. These diseases not only reduce yields and contribute to food insecurity but also deepen social inequalities by disproportionately affecting small-scale farmers in developing regions [1]. Additionally, conventional plant disease management relies heavily on synthetic fungicides, which pose risks to human health and the environment [2].
In recent years, the growing resistance of plant pathogens to conventional control measures has underscored the need for alternative disease management strategies that reduce chemical inputs. The losses caused by bacterial diseases are substantial, affecting nearly one-third of total food production [3]. The environmental impact is equally significant, as bacterial plant diseases can lead to reduced crop yields, resource waste, soil degradation, and deforestation. These effects arise because the reduction in available food and agricultural inputs increases pressure on land and natural resources, often leading to land conversion and the overexploitation of ecosystems [4,5]. This is particularly evident in the case of energy-intensive crops like onions [6]. Together, these challenges emphasize the need for alternative disease management strategies that reduce chemical inputs and maintain food quality [6]. Among emerging alternatives, bacteriophages offer a promising approach to addressing plant bacterial diseases. As viruses that selectively target and destroy bacterial pathogens, phages provide a natural and highly specific means of disease control. Their ability to evolve alongside bacterial hosts reduces the likelihood of resistance, making them a viable long-term strategy.
In this review, we explore the benefits and challenges of the use of bacteriophages as biocontrol agents in agriculture. Their advantages over traditional methods and the challenges associated with their application in plant protection and bacterial disease management. Although this review focuses on bacteriophage applications in managing post-harvest diseases, it is important to recognize that effective plant protection encompasses the entire growth cycle. Bacteriophages have shown promise in controlling bacterial pathogens during both the growing season and post-harvest storage, addressing disease origins at multiple points. We discuss the specific plant diseases that bacteriophages can address and how their use can reduce reliance on chemical pesticides and improve food quality and safety. Previous reviews have predominantly focused on the use of bacteriophages in food safety applications, such as meat, dairy, and Listeria control, or on fungal postharvest pathogens [6,7]. In contrast, this review specifically addresses the application of bacteriophages in the management of diseases of fruits and vegetables. By integrating the biological mechanisms of phages with practical challenges, formulation strategies, and regulatory barriers, this work aims to provide a comprehensive perspective on their potential as sustainable alternatives for bacterial plant disease control.

2. Benefits of Using Bacteriophages as Biological Control Agents

Both bacteriophages and phage-derived lytic proteins play crucial roles in ensuring food safety throughout the food chain, from farm to fork [6]. By leveraging their natural bactericidal properties, these agents provide an environmentally friendly alternative for disease management, thereby reducing the reliance on traditional antibiotics and pesticides [6]. This approach helps to preserve beneficial microbial communities while contributing to sustainable agricultural practices and enhancing food safety [8,9].
Traditional methods of protection against storage diseases rely on synthetic compounds, which may negatively impact crops, soil, and air. In contrast, bacteriophages, as highly specific bacterial viruses, do not leave harmful residues in the environment, aligning with the concept of green chemistry [10,11]. Unlike broad-spectrum chemicals, bacteriophages minimize the risk of disturbances in the soil microbiome. Due to their specificity, bacteriophages only target pathogenic bacteria, leaving beneficial bacteria, such as plant growth-promoting bacteria (PGPB), unaffected [12].
The specificity of bacteriophages is mediated by their receptor-binding proteins (RBPs), which recognize bacterial surface receptors to initiate infection. For instance, the RBPs of Listeria phage A511 can recognize and bind to multiple serotypes of Listeria monocytogenes by targeting different wall teichoic acid (WTA) structures, allowing effective adsorption and subsequent infection [13]. In agriculture, bacteriophages are employed as biocontrol agents to combat bacterial diseases in crops. Unlike chemical pesticides, phages target specific pathogens without harming non-target organisms, thereby preserving ecological balance and reducing the risk of resistance development. Phages have been successfully used against phytopathogens such as Xanthomonas campestris and Pseudomonas syringae, which cause substantial crop losses. Phage cocktails, combining multiple phages, have proven particularly effective in addressing the adaptability of bacterial pathogens [11,14].
Bacteriophages exhibit diverse host ranges. They may target one bacterial strain, multiple strains within the same species, or even different bacterial species and genera. For instance, the phage Pg125 is a polyvalent phage of Xanthomonas, capable of lysing numerous strains across 25 species of this genus [15]. Additionally, the novel bacteriophages of Kosakonia cowanii, strain bonnellvirus (Kc261) and novel sortsnevirus (Kc237), have narrow host ranges, but the novel kayfunavirus (Kc166A) and novel cronosvirus (Kc318) lyse both plant and human K. cowanii strains, making them promising for use as bio-curative tools in either plant protection or medicine [16].
Phage cocktails constitute a sustainable technology for targeting foodborne pathogens and spoilage bacteria. Bacteriophages are highly specific, usually targeting only one species or type of bacteria, which means they do not disrupt the natural microbiota in the gastrointestinal tracts of humans and animals. Additionally, bacteriophages have shown no adverse or toxic effects on eukaryotic cells [17]. These viruses are naturally found in many food products, soils, and water environments, and they do not alter the sensory qualities of food [18]. They are also highly resistant to the stresses of food processing, such as high temperatures or pH changes, which makes them suitable for food safety applications. This has been confirmed by [19], who successfully isolated bacteriophages from soil and applied them to various food products including rice, milk, meat, and lettuce without affecting their sensory properties.
The long history of safe use of bacteriophages, combined with their natural ubiquity in food environments and animals, supports their use as biological control agents. Phage therapy has recently regained attention due to its excellent safety profile in preclinical and clinical studies, with minimal adverse effects reported in humans and animals [20]. Phages remain highly specific to bacterial targets, sparing beneficial microbiota and mammalian cells, supporting their harmlessness to humans and potential to maintain microbiome balance [21]. Their ability to self-replicate within bacterial hosts ensures sustained antibacterial effects, confirmed by systematic reviews demonstrating efficacy against multidrug-resistant and biofilm-forming bacteria [22,23].
Moreover, phage-derived enzymes such as depolymerases and endolysins have boosted effectiveness against biofilms, which are often resilient to conventional antimicrobials [24,25]. Phages are genetically tractable, with advances in bioengineering enabling tailored phage cocktails for complex infections and food safety applications [20]. Currently, phages serve not only therapeutic roles but also as tools for pathogen detection and as sources of novel antimicrobials effective against the bacterial cell wall [24,25]. These developments highlight the versatility of bacteriophages in clinical, agricultural, and food safety contexts.
Endolysins, bacteriophage-derived enzymes, have emerged as a promising antimicrobial alternative in food safety applications. Unlike whole phages, endolysins directly degrade bacterial cell walls, leading to rapid lysis of Gram-positive bacteria within minutes. These enzymes do not facilitate horizontal gene transfer or antibiotic resistance development, making them a safer alternative for controlling foodborne pathogens [26].
Bacteriophages demonstrate an excellent safety profile for biocontrol applications. They are naturally ubiquitous in food products, soils, and water environments [27] and they do not alter the sensory qualities of food [28,29,30]. Importantly, phages have shown no adverse or toxic effects on eukaryotic cells or mammalian cells, maintaining microbiome balance due to their high specificity to bacterial targets [31]. Endolysins, as phage-derived antimicrobial alternatives, enhance safety because they directly degrade bacterial cell walls and do not facilitate horizontal gene transfer or antibiotic resistance development [32]. However, continuous research is needed to fully understand the long-term ecological impacts of large-scale phage applications on natural microbial communities.
Beyond their applications in food safety, bacteriophages and their derivatives, such as endolysins, may also support environmentally responsible agriculture and ecosystem management. Introducing bacteriophages into natural ecosystems, including soil and plants, could help control bacterial pathogens, improve plant health, and maintain soil microbial balance. Bacteriophages can effectively target pathogenic bacteria, enhancing plant health and soil quality by reducing microbial contaminants. Their potential use in bioremediaton supports the degradation of microbiological pollutants, which contributes to the restoration of ecosystems and the maintenance of soil productivity [9].
However, concerns have been raised regarding the long-term ecological impacts of large-scale bacteriophage applications. Alterations in the natural soil microbial community could reduce microbial diversity and disrupt vital processes like nitrogen cycling and organic matter decomposition, with downstream effects on soil fertility and ecosystem resilience. Thus, further research is crucial to fully understand long-term interactions between bacteriophages, soil microorganisms, and plant health, to ensure safe and effective applications [33].
Recent research also highlights growing interest in phage cocktails and engineered phages for diverse food safety and agricultural uses, with ongoing studies emphasizing improved efficacy, stability, and regulatory compliance [6,9,18,20,21].

3. Challenges and Limitations in Phage Application

Despite the promising advantages of bacteriophages in bacterial control, several challenges hinder their widespread application. Among the most significant concerns is biosafety, particularly regarding bacterial resistance to phages. While bacterial resistance to phages develops at a lower frequency than antibiotic resistance, it remains a critical issue that must be addressed [34,35]. Phages replicate quickly, producing about 100–200 new viral particles per cycle compared to bacterial binary fission; still, they do not fully eliminate bacterial populations. Both phages and bacteria have developed defense strategies that enable their mutual coexistence, leading to continuous coevolution. Understanding these interactions is vital for grasping bacterial population dynamics in both natural and controlled environments [36].
These defense mechanisms are crucial for bacterial survival and can be broadly categorized into several types, each with unique methods of action. The key mechanisms are: restriction–modification systems, inhibition of capsule production and lysogenization, inhibition of phage adsorption, blocking DNA injection, abortive infection, toxin-anti-toxin system, and bacteriophage assembly interference. Besides biosafety issues, an additional challenge is posed by phages’ environmental stability and economic and practical constraints of their usage.

3.1. Internal Bacterial Defense Mechanisms Against Phages

When bacterial cells are unable to prevent the injection of phage DNA, multiple internal defense systems are activated. These systems typically consist of a sensor to detect infection and an effector that either targets the phage or eliminates the infected host before the phage reproduction cycle is completed, thereby protecting the remaining cellular population from newly released viral particles [37].

3.1.1. Restriction–Modification System (RM)

Restriction–modification systems are crucial for bacterial defense against bacteriophages. These systems include restriction endonucleases that cut specific DNA sequences in phage DNA and methyltransferases that protect bacterial DNA by adding methyl groups to the same recognition sites. RM systems are classified into four types based on their mechanisms and structures. The interaction between restriction endonucleases and methyltransferases exemplifies an evolutionary arms race between bacteria and phages. For instance, recent studies on the plant pathogen Xylella fastidiosa revealed the presence of multiple type I RM systems that contribute to defense against invading genetic elements. In particular, the specificity subunits (hsdS) of these systems show extensive allelic diversity through recombination of target recognition domains (TRDs), resulting in differential DNA methylation patterns across strains. Such methylation modifications can prevent the replication of foreign DNA, including that of bacteriophages, without necessarily cleaving it, akin to mechanisms observed in BREX or DISARM systems in other bacteria [38,39,40]. This highlights the importance of epigenetic modifications in bacterial immunity and illustrates the evolutionary arms race between phages and their plant-pathogenic hosts. Apart from the restriction–modification system, bacteria possess other defense mechanisms that function similarly by recognizing and defending against foreign nucleic acids through methylation of host DNA (Table 1).

3.1.2. Inhibition of Capsule Production and Lysogenization

One of the primary strategies bacteria use to defend against phages involves the inhibition of capsule production and lysogenization (Table 1). Initially, bacterial resistance emerged through mutations that inhibited capsule biosynthesis, allowing bacteria to survive under high phage pressure. Over longer evolutionary timescales, capsulated cells became more frequent as bacteria fine-tuned capsule production to better evade phage attacks. This dynamic interaction underscores the trade-offs associated with different resistance mechanisms. While lysogenization can confer resistance to phages, it often incurs a high fitness cost due to the risk of prophage induction, which can lead to cell death [41].

3.1.3. Inhibition of Phage Adsorption

This mechanism is based on preventing phage attachment to the bacterial cell membrane. Biofilms act as a protective barrier that limits phage access, while Gram-negative bacteria release outer membrane vesicles (OMVs) that can trap phages and block their interaction with host cells. For instance, Gram-negative plant-associated bacteria, including endophytic and pathogenic species, release OMVs to interact with their host plants, facilitating colonization and molecular communication while potentially limiting phage access to the bacterial cell. These OMVs can carry proteins, toxins, and signaling molecules into plant tissues or environmental niches inaccessible to whole bacterial cells, illustrating how OMVs serve both ecological and defensive functions [42].
Another key defense involves altering or eliminating surface receptors that phages use for attachment. Modification or loss of outer membrane structures and surface receptors represents a key defense strategy of plant pathogenic bacteria against phage infection, directly affecting the first step of the infection process—phage adsorption [43]. The main surface components acting as phage receptors include lipopolysaccharides (LPS), extracellular polysaccharides (EPS), outer membrane proteins, pili, and flagella. Alterations in these structures can prevent phage attachment but often come with physiological or virulence costs to the host. In Pseudomonas syringae pv. tomato, mutations in the rfbD and rfbA genes involved in LPS biosynthesis lead to changes or loss of phage-binding sites, conferring resistance to specific phages [44]. Similarly, in Pseudomonas syringae pv. porri, resistance to a two-phage cocktail was linked to mutations in LPS metabolism genes, confirming that LPS acts as the main receptor for these phages [45]. In Erwinia amylovora, the infectivity of Myoviridae and Podoviridae phages depends on the amount and composition of EPS produced by the host—Myoviridae phages preferentially infect hosts producing low or acidic EPS, whereas Podoviridae phages are more efficient against strains with high or neutral EPS [46]. In Xanthomonas spp., resistance mechanisms are also based on structural alterations. A mutation in the glycosyltransferase gene CDS2289 in Xanthomonas oryzae pv. oryzae (Xoo) confers resistance to phage X2 by modifying the LPS profile, which reduces virulence as a trade-off [47]. Likewise, a mutation in the xanA gene in Xanthomonas campestris has been shown to decrease phage adsorption efficiency. Moreover, studies have confirmed the presence of a functional CRISPR/Cas system in X. oryzae, providing an additional adaptive immunity mechanism against phage infections. The details are summarized in Table 1.

3.1.4. Blocking DNA Injection

Even when a bacteriophage successfully attaches to a bacterial cell, the Superinfection Exclusion (SIE) system can prevent the injection of its DNA, blocking the infection process. This defense mechanism works at different stages of the infection: it can stop further phage attachment early on or interfere with the DNA injection in the later phase. As the proteins responsible for SIE are typically encoded by prophages, this system is considered a form of interaction between phages. Most of these SIE proteins are either integrated into the bacterial membrane or associated with membrane structures [37,48].
In the context of plant pathogenic bacteria, the presence of prophages and SIE mechanisms is particularly relevant when considering phage-based biocontrol strategies. Temperature (lysogenic) phages are generally regarded as less suitable for biocontrol purposes because they can contribute to the dissemination of virulence factors through transduction, potentially enhancing bacterial pathogenicity. Moreover, prophage-encoded SIE systems may prevent subsequent infections by virulent phages, reducing the overall effectiveness of biological control. Some lysogenic phages also harbor genes that increase the virulence or fitness of their host bacteria, while their ability to lyse and eliminate bacterial cells is typically lower than that of strictly lytic phages. For these reasons, the application of lytic phages is preferred for the control of plant pathogenic bacteria [43,49].

3.1.5. Abortive Infection

Abortive infection (Abi) (Table 1) is a bacterial defense mechanism that induces controlled cell death or dormancy in a phage-infected cell before the virus can complete its replication cycle. By halting the release of new viral particles, Abi protects the surrounding clonal bacterial population from widespread infection. Although the concept of programmed cell death in prokaryotes was once controversial due to their unicellular nature, microbial populations often exist as genetically identical communities, making altruistic suicide a viable evolutionary strategy. Since most bacteriophages have a narrow host range, Abi primarily benefits related cells by preventing phage propagation within the population [41].
Recent studies have highlighted the relevance of Abi systems in plant-pathogenic bacteria, particularly in the context of phage therapy [44] provided a comprehensive overview of bacteriophage applications in controlling bacterial plant diseases and emphasized the role of bacterial defense mechanisms, including Abi, in shaping phage-host dynamics. Although Abi systems were historically studied in dairy fermentation strains such as Lactococcus lactis, their presence in phytopathogens like Pectobacterium atrosepticum, which harbors the ToxIN system, demonstrates that plant pathogens also employ altruistic suicide strategies to limit phage propagation. These systems pose both a challenge and an opportunity for phage-based biocontrol, as understanding and circumventing Abi responses may enhance the efficacy of phage therapy in agricultural settings [45].
Most defense systems that involve regulated cell death consist of two main modules: the phage-sensing module, which detects the presence of an infection, and the effector module, which triggers cell death or growth arrest upon activation by the phage-sensing module. These modules are often found in separate proteins. For instance, in the CBASS, Pycsar, and Thoeris systems, the phage-sensing module is linked to an enzymatic domain that generates a signaling molecule upon phage detection. The cell-killing module, encoded by a different protein, then induces cell death when it binds to the signaling molecule. In other systems, such as Avs, CapRel, and DSR proteins, the phage-sensing and cell-killing domains are part of the same protein. In these cases, phage detection causes a conformational change that activates the cell-killing domain [46].
The Abi system can detect various stages and components of phage infection, including phage genome replication, early and late phage structural proteins, phage proteins expressed in the cytosol during replication, a broad spectrum of phage DNA transcripts, and the phage-induced shutdown of host gene expression [47]. The Abi system can also be combined with the CRISPR-Cas system to exert a strong anti-phage effect. The type III CRISPR-Cas system recognizes phage mRNA exported from the nucleus, which activates NucC, a cyclic triadenylate-dependent accessory nuclease. Although the CRISPR-Cas system cannot access the phage DNA in the nucleus, it degrades bacterial chromosomes, inhibits phage maturation and replication, and triggers cell death. Thus, type III CRISPR-Cas-mediated immunization against phages occurs via Abi [50]. The death of host cells during phage infection is generally not primarily due to the activation of the Abi mechanism, but rather the result of extensive and irreversible damage caused by the phages to the host genome. However, Abi defense strategies are initiated when phage infections become particularly difficult to control or when phages develop resistance to other host defense mechanisms [37].

3.1.6. Toxin–Antitoxin System

Toxin–antitoxin (TA) systems (Table 1) are genetic elements found in most bacterial and archaeal genomes, with individual species often encoding numerous distinct systems. Despite their widespread presence, the functions of TA systems have remained poorly understood and sometimes controversial. However, there is growing evidence that they play crucial roles in protecting bacteria against their ubiquitous and relentless predators, bacteriophages. TA systems typically consist of a protein toxin that inhibits host cell growth, often reversibly, unless restrained by its corresponding antitoxin [37]. The antitoxins in Type I systems are antisense RNAs that block toxin synthesis, and the toxins are usually small peptides that create membrane pores, disrupting the proton motive force needed for ATP synthesis. Type II systems, the most extensively studied, consist of an antitoxin protein that directly binds and neutralizes its corresponding toxin. These antitoxins often have a DNA-binding domain that negatively autoregulates their own transcription. Type II toxins include endoribonucleases targeting mRNA, rRNA, and tRNA; ribosome-poisoning proteins; acetyltransferases targeting tRNAs; topoisomerase inhibitors; (p)ppGpp/(p)ppApp synthetases; tRNA pyrophosphorylating proteins; mono-ADP-ribosyltransferases; and cell wall inhibitors. Type III systems feature an RNA antitoxin that directly binds and neutralizes its corresponding toxin, with all known type III toxins being endoribonucleases. Type IV systems consist of an antitoxin protein that indirectly antagonizes the enzymatic activity of its corresponding toxin rather than directly binding it. These toxins include DNA ADP-ribosyltransferases, predicted nucleotidyltransferases, FtsZ inhibitors, and ppGpp/ppApp synthetases. While these classifications provide a useful framework, some TA systems do not fit neatly into any of these categories [51].
Currently, TA systems are categorized into eight types according to the detailed mechanism of the antitoxin involved [37]. In type V TA systems, the antitoxin GhoS acts as a specific RNase that breaks down the toxin mRNA. Conversely, in type VI TA systems, the antitoxin protein functions as a proteolytic adapter, promoting the degradation of the toxin SocA. In type VII TA systems, the antitoxin neutralizes toxin proteins through chemical modifications. Lastly, in type VIII TA systems, the small RNA toxin CreT sequesters tRNAUCU, while the crRNA-like antitoxin CreA directs the transcription of Cas proteins to inhibit the CreT toxin [52]. In plant-pathogenic bacteria, Type III TA systems have been documented, with the toxIN module in Pectobacterium atrosepticum being the first identified example. In this system, the ToxN protein functions as an endoribonuclease, while the ToxI RNA antitoxin interacts directly with ToxN to form a trimeric complex that neutralizes the toxin. The ToxI RNA is composed of repeated sequences that serve as key structural features for its antitoxic function. Functionally, toxIN provides protection against bacteriophage infection through an abortive infection mechanism, promoting altruistic cell death to limit phage propagation [53].

3.1.7. Bacteriophage Assembly Interference

The next defense mechanism is bacteriophage assembly interference (Table 1), a strategy employed by bacteria to disrupt the assembly of bacteriophages, thereby preventing their successful replication. One example of this mechanism involves phage-induced chromosomal islands (PICIs), which are mobile genetic elements commonly found in bacteria. When a Gram-positive bacterium is infected by a helper phage, the PICI is excised from the bacterial genome, altering the size of the phage capsid and favoring the packaging of the PICI gene cluster, thus hindering normal phage assembly. In contrast, in Gram-negative bacteria, PICIs are activated by a PICI-encoded activator, but this activation depends on the presence of helper phages [37]. While the major plant-pathogenic bacteria genera include both Gram-negative and Gram-positive species, explicit reports of PICIs in classical plant pathogens are limited. However, the fact that some plant pathogens are Gram-positive suggests that PICI-mediated phage interference could, in principle, operate in these species, whereas Gram-negative plant pathogens may rely on other mobile genetic or phage defense strategies [54,55].

3.2. Environmental Stability

The application of bacteriophages in agriculture and food storage involves several challenges and limitations, including technical, economic, and biosafety concerns. Despite notable successes, obstacles such as understanding phage-host dynamics, ensuring long-term stability, and managing environmental risks like horizontal gene transfer remain to be addressed [56]. Emerging trends point toward integrating phages with prebiotics, biostimulants, or traditional management strategies to enhance their effectiveness. Advances in genomic and metagenomic technologies are enabling researchers to design phage applications tailored to specific microbial targets, allowing more precise and effective control of bacterial pathogens. These developments underscore the importance of continued research to close existing knowledge gaps, optimize phage-based interventions, and unlock their full potential for bacterial diseases and ecosystem management [56].
Despite these advances, some challenges remain, such as the specificity of phages, the need for precise pathogen identification, and the ability to scale phage treatments across different agricultural systems. Additionally, even with preventive measures, minor cases of soft rot were still detected after potatoes were packaged and sent to retail stores. The study also revealed phage-resistant strains and other bacteria with pectolytic activity, underscoring the complexity of managing soft rot in potatoes. These findings suggest that while phage treatment can significantly reduce bacterial populations, it may need to be part of a broader integrated management strategy for maximum effectiveness [57]. While phages have demonstrated effectiveness in bacterial plant disease applications, their performance during the growing season has been less consistent. Most successful trials have been conducted after harvest, underscoring the need for further research into the efficacy of phages during active plant growth. The absence of standardized protocols for evaluating phage effectiveness complicates the comparison of results across studies. Therefore, developing standardized testing methods is crucial to fully assess the potential of phages in agricultural practices [58]. An innovative approach to bacteriophage production is the two-stage, self-cycling process, which enhances both the efficiency and sustainability of phage manufacturing [59]. This method involves a bioprocess where the phage production and host cell lysis occur in distinct stages, optimizing the conditions for each phase to maximize yield. By cycling through these stages, the process can continuously produce high concentrations of phages with minimal downtime and resource input. This is particularly relevant for agricultural applications, where large-scale and cost-effective production of phages is necessary for practical implementation. Not only does this method reduce production costs, but it also ensures a consistent supply of high-quality phages, crucial for the reliable biological control of bacterial plant diseases [59].
The main technical challenge is the limited durability of phages in the environment, which is particularly important for the fruit and vegetable industry, requiring a distinct approach compared to the meat or dairy sectors. Several factors can reduce the effectiveness of phage treatments, including plant watering, washing of ready-to-eat products (which can dilute the doses), UV radiation, and the spread of phytopathogens by wind, insects, or humans. Additionally, anomalous weather conditions and environmental factors such as variable pH, temperature, solar radiation (particularly UV-A and B), desiccation, and exposure to pesticides like copper-based bactericides can significantly impact phage persistence in crops and overall yields [44,49,60,61]. Among these factors, solar radiation is the most harmful, with phage populations on tomato leaf surfaces dropping from approximately 109 PFU/g of tissue to undetectable levels over a 6 h period during peak UV radiation in the early afternoon. However, applying bacteriophages in the late afternoon or early evening near sunset improves their overnight persistence, allowing larger phage populations to interact with bacterial strains on the leaf surface. In studies on phage survival in the rhizosphere and their translocation into stems, phages applied to soil around tomato plants were detected in foliar tissues at levels of 106–107 PFU/g of plant tissue in the upper leaves and stems two days after application. Phage populations fell below detectable levels by the seventh day in plants with damaged roots and by the fifteenth day in plants with undamaged roots. Although phages persisted in the rhizosphere and roots of treated plants, their numbers declined by ten- to a hundred-fold over a 14-day period [49]. However, it has to be acknowledged that the effectiveness of phages in field conditions can vary compared to laboratory studies [35].

3.3. Regulatory Hurdles and Biosafety

Another challenge in the field of phage research and application in agriculture lies in regulatory hurdles and biosafety, which both generate economic and practical constraints. The situation is twofold. Many countries lack clear regulatory frameworks for phage-based products or, in contrast, countries like the United States with its Environmental Protection Agency (EPA) enforce stringent requirements for data on microbial pesticide residues, toxicology, effects on non-target organisms, and environmental fate. These tests are costly and typically beyond the financial capacity of government or university laboratories, meaning they are primarily funded by private companies aiming to commercialize the antagonists. Moreover, some phage cocktails may require regular updates to remain effective, which could necessitate re-approval processes [62]. However, ensuring the safety of biological control treatments is crucial when developing commercial products. Nevertheless, for those reasons, small companies may hesitate to invest in registering new antagonists if their use is limited to specific diseases or minor commodities, as the return on investment could take too long [63]. The registration costs could be significantly reduced if the EPA adopted a system similar to the European Food Safety Authority’s (EFSA) Qualified Presumption of Safety (QPS). Under this system, any antagonist strain identical to one in the QPS group would not require further safety assessment. This group includes microorganisms used in food production and preservation that have been widely consumed. The QPS list is regularly updated with new microorganisms that are well-characterized and deemed safe. While isolating antagonists from fruit surfaces does not automatically confirm their safety, many of these microorganisms have been part of our diet for many years. Establishing a QPS-like list in the United States would remove a significant barrier to registering new antagonists, promote the use of biological control for bacterial diseases, and encourage more research on listed microorganisms by increasing their commercialization potential [63]. Next to regulatory hurdles, the isolation, study and production of phages is associated with substantial financial burdens. Certain phage-based products require specialized storage and transportation conditions, such as cold chain logistics, which can increase operational complexity and costs. The effective deployment of phages in complex environments, within soil matrices, presents technical hurdles that researchers are still working to overcome [35]. For this reasons, scaling up phage production and purification to industrial levels while following good manufacturing practices remains a significant challenge. That is why developing stable phage formulations for different applications such as sprays or washes is difficult [64]. One of the ways to address the above issues is microencapsulation, which provides protection for encapsulated phages and ensures their gradual release into the food matrix. Finally, the greatest concern remains biosafety. Society is still worried about the potential development of bacterial resistance to phages, although it occurs at lower rates compared to antibiotic resistance [34,35]. Bacteriophage resistance in bacteria is one of the main concerns regarding bacteriophage-based biocontrol strategies, particularly in agricultural applications, as reviewed by [65]. A detailed understanding of bacterial resistance to bacteriophages and their interaction with plants plays an important role in the design of bacteriophage-based biocontrol strategies of bacteria. There are also concerns about the potential effects on non-target bacteria in microbial communities, though many phages have a narrow host range and infect only a limited number of bacterial strains [29]. Safety concerns hinder the widespread adoption of phage-based products. Additionally, introducing high concentrations of phages into the environment due to its potential to mediate horizontal gene transfer of undesirable traits between bacteria. The immunogenicity of phage proteins in animals is another issue to consider.
Given the above, there is an ongoing need for public education and awareness campaigns to foster consumer acceptance of phage-based products and technologies [35]. Addressing these multifaceted challenges through further research, adaptation of regulations, and education efforts will be key to expanding the use of phages as eco-friendly antimicrobials in agriculture and food safety applications. Despite the limitations, phages show promise as alternatives to conventional antimicrobials, but more work is needed to overcome the current obstacles to their widespread adoption [35,61,62].
Figure 1 summarizes the key practical constraints influencing the effectiveness of bacteriophage-based biocontrol, including factors related to production and logistics, application, environmental stability, and bacterial interactions.

4. Bacterial Plant Diseases Addressable by Bacteriophages

In a recent case study, Ref. [57] isolated pectolytic bacterial strains from rotting potato tubers and stems were used. Phages with a broad host range were selected and formulated as a cocktail, which significantly reduced bacterial concentrations in a warehouse environment. In laboratory assays, T4-like phage cocktails were found effective against Dickeya solani, reducing the incidence and severity of soft rot in potatoes [66]. Additionally, phages targeting Pectobacterium atrosepticum have been shown to prevent the rotting of harvested potatoes [67]. These findings highlight the potential of phage therapy to control soft rot caused by various pectolytic bacteria in storage [60]. Phages against Pectobacterium carotovorum and Dickeya solani have demonstrated up to an 80% reduction in soft rot severity, underscoring the importance of phage therapy in managing storage diseases [60]. The summary of the effectiveness of phage therapy in plant disease control is presented in Table 2.
A different study by [68] isolated and characterized six bacteriophages from processing water samples, identified as members of the Podoviridae and Myoviridae families. These phages effectively lysed Pectobacterium spp., with φMA2 showing the broadest host range. Phage stability was tested under various conditions, with some maintaining efficacy under extreme temperatures and UV exposure. In vitro and semi-in planta, (which means the test was conducted on potato tubers) tests demonstrated that the phage cocktail reduced bacterial growth and tissue maceration in potato tubers. Field trials further confirmed its effectiveness in reducing soft rot compared to controls, highlighting phages as a promising biocontrol strategy for plant storage diseases [68]. Moreover, the phage PP1 was effective in controlling Pectobacterium carotovorum subsp. carotovorum in lettuce, with over 80% of seedlings showing no disease symptoms when applied via foliar spraying post-infection [69]. Also, Pseudomonas syringae pv. porri, which causes bacterial blight in leeks, has been targeted by bacteriophages with promising results [70]. Phage therapy was shown to reduce lesion length and improve the storage life of leeks.
Furthermore, phages targeting Pseudomonas species responsible for spoilage in crops have been explored as biocontrol agents. These phages specifically target spoilage bacteria without affecting beneficial microbiota, providing an environmentally responsible alternative to traditional chemical treatments [70]. For instance, phages have been shown to mitigate spoilage caused by Pseudomonas in stored vegetables and fruits, extending their shelf life without causing environmental damage. This targeted approach reduces reliance on chemical pesticides, which are increasingly scrutinized for their environmental and health impacts [44].
The pathogen Xanthomonas oryzae pv. oryzae, which causes bacterial leaf blight (BLB) in rice, has traditionally been managed through seed disinfection with traditional synthetic pesticides. However, this method can lead to environmental contamination and pesticide residues [71]. Bacteriophage therapy has emerged as a promising alternative, with phages demonstrating effectiveness in disinfecting seeds without harming plant health. Moreover, phages targeting Xanthomonas have been employed in managing bacterial spot and wilt diseases in fruits like citrus, as well as other crops like walnuts and leeks [72]. This method offers an eco-friendly alternative to chemical treatments, reducing pesticide dependence [49].
In contrast, phage application targeting Xanthomonas arboricola pv. juglandis in walnuts (Payne cultivar) via bud spraying resulted in poor phage survivability and no significant disease suppression. Moving beyond Xanthomonas, phages ΦRSA1, ΦRSB1, and ΦRSL1 effectively mitigated Ralstonia solanacearum in tomatoes through pre-infection plant soaking, with ΦRSL1 preventing wilting symptoms. For Streptomyces scabies on potatoes (Kennebeck cultivar), immersion of tubers in phage ΦAS1 resulted in a significant decrease in lesion number and surface area [73,74]. In another study on R. solanacearum, the causative agent of bacterial wilt, which severely affects crops such as tomatoes and peppers, phage therapy has shown success in managing this pathogen, particularly with phages such as φRSA1, φRSB1, and φRSL1. These phages have been shown to reduce wilt severity in tomatoes [74]. Phage therapy with φRSL1 was also found to extend the healthy lifespan of plants by preventing wilting symptoms. Moreover, phages like φRSA1 have been effective in reducing bacterial wilt symptoms in tomatoes and peppers. The application of phages against Ralstonia can also improve the storage life of produce by controlling bacterial wilt during storage [74].
Research conducted by [75] delves into recent advancements in phage-based applications, emphasizing their potential to control bacterial threats in plants and agricultural environments. Experimental trials have confirmed the effectiveness of phages in mitigating bacterial wilt caused by R. solanacearum, a pathogen notorious for inflicting severe damage on crops like potatoes, tomatoes, and peppers. Field studies further showcase phage therapy’s ability to suppress spoilage bacteria in stored produce, thereby enhancing shelf life and preserving quality. Finally, phage application directly to the rhizosphere of tomatoes suppressed wilting caused by R. solanacearum, highlighting the diverse applications and outcomes of bacteriophage-based approaches in plant pathogen control [76].
Bacteriophages have proven effective in managing a variety of plant pathogens in post-harvest environments. For instance, phages targeting Xanthomonas axonopodis pv. citri have been shown to reduce disease severity in citrus fruits by 59% [72]. Similarly, phages targeting Xanthomonas arboricola pv. juglandis have been used to control walnut blight, although their effectiveness in long-term survivability remains a challenge [72].
Bacteriophages represent a promising biocontrol solution for bacterial diseases caused by Erwinia, Pseudomonas, and Xanthomonas. The summary of the studies on the use of phages in plant disease control and the reduction of spoilage of plant products is presented in Table 2. They provide an environmentally friendly alternative to traditional chemical treatments, reducing pesticide reliance and promoting sustainable agricultural practices. The use of bacteriophages decreases the dependence on synthetic pesticides during the storage and transport of fruits and vegetables, which is particularly relevant for crops with strict residue limits in export markets. However, further research is necessary to optimize phage formulations, application methods, and strategies for commercial use. As phage therapy continues to evolve, it holds significant potential for improving crop health, extending shelf life, and enhancing the sustainability of food production [77].
A study by [78] demonstrated that employing phages to inhibit bacterial growth responsible for crop spoilage could result in increased economic profits and enhanced control over the vegetable market [78]. The results revealed significant variability in microbial loads, with tomatoes showing the highest load, followed by grapes and mushrooms. Green peppers and lettuce had moderate loads, while spinach and apples had the lowest. Bacterial identification highlighted the presence of both Gram-positive and Gram-negative bacteria. Antibiotic susceptibility tests indicated varying resistance levels. Phage therapy showed potential as a biopreservation method by effectively reducing microbial loads, particularly those caused by antibiotic-resistant strains [78].
All of the above-described studies have shown that during phage therapy, the accompanying flora was preserved. This supports the view that phage therapy in agriculture is an environmentally friendly approach that also reduces reliance on chemical plant protection products. It is important to note that many bacterial plant diseases originate during plant development in the field. These pathogens can persist in plant tissues and affect plant health throughout the growing season. Therefore, control strategies and research frequently focus on pathogens relevant to various stages of plant growth and disease progression (Table 2).
Table 2. Overview of studies on phage therapy for plant disease control.
Table 2. Overview of studies on phage therapy for plant disease control.
DiseasePathogenPlantMethodOutcomeSource
Citrus DiseasesXanthomonas axonopodis pv. citriGrapefruit (Duncan cultivar)Evening foliar application before infection59% reduction in disease severity[72]
Tomato DiseasesRalstonia solanacearumTomato (Oogata-Fukuju cultivar)Plant soaking pre-infectionPrevention of wilting symptoms with phage ΦRSL1[74]
Potato DiseasesStreptomyces scabiesPotato (Kennebeck cultivar)Tuber immersionSignificant reduction in lesion number and surface area[73,74]
Leek DiseasesPseudomonas syringae pv. porriLeekField trial with foliar applicationReduced lesion length and improved storage life[70]
Lettuce DiseasesPectobacterium carotovorum subsp. carotovorumLettuceFoliar spraying post-infectionOver 80% of seedlings showed no disease symptoms[69]
Potato DiseasesPectolytic bacteriaPotatoApplication in storageReduction in bacterial concentrations in the warehouse[57]
Potato DiseasesDickeya solaniPotatoT4-like phage cocktailsReduction in the incidence and severity of soft rot[66]
Potato DiseasesPectobacterium atrosepticumPotatoApplication before storagePrevention of rotting[67]
Potato DiseasesPectobacterium carotovorum, Dickeya solaniPotatoPhage cocktail applicationUp to 80% reduction in soft rot severity[60]
Potato DiseasesPectobacterium spp.PotatoPhage cocktail applicationReduction un bacterial growth and tissue maceration[68]
Diseases of Potatoes, Tomatoes, PeppersRalstonia solanacearumPotatoes, tomatoes, peppersApplication in stored productsReduction in bacterial wilt[75]
Tomato DiseasesRalstonia solanacearumTomatoPhage application in the rhizosphereReduction in wilting symptoms[76]
Product SpoilageStaphylococcus aureus, Bacillus sp., Lactobacillus sp., Streptococcus sp., E. coli, Klebsiella sp., Enterococcus faecalisVarious vegetables and fruits (tomatoes, grapes, mushrooms, green pepper, lettuce, spinach, apples)Phage applicationReduction in spoilage bacteria, extended shelf life[78]

5. Conclusions

The study of bacteriophages has advanced our understanding of bacteria–virus interactions and opened possibilities for their application in managing plant diseases. Phage specificity in targeting pathogens positions them as a promising alternative to conventional antimicrobials, particularly in the context of increasing antibiotic resistance. Despite their potential, several knowledge gaps remain. Large-scale field studies evaluating phage efficacy under commercial postharvest conditions are limited, and the long-term stability of phages during storage, transport, and variable environmental conditions is not fully understood. Moreover, there is insufficient data on the ecological impacts of phage applications on microbial communities in fruits, vegetables, and storage environments. Standardized protocols for phage formulation, application, and assessment are also lacking, limiting their practical adoption.
This review contributes novel insights by specifically focusing on bacterial postharvest pathogens, integrating fundamental phage biology with practical challenges, formulation strategies, and regulatory considerations. Unlike previous reviews that have primarily addressed preharvest applications, general food safety, or fungal postharvest diseases, this work emphasizes the unique opportunities and limitations of phage-based solutions for postharvest bacterial disease management.
Future research should aim to improve phage stability under varying environmental conditions and develop strategies to mitigate resistance. Regulatory frameworks also need refinement to support the safe and effective use of bacteriophages in agriculture. By overcoming these challenges, bacteriophages have the potential to become a viable, environmentally responsible alternative to traditional chemical treatments, contributing to more sustainable food production and preservation.

Author Contributions

All authors contributed to the conception and design of the review. Literature search, analysis, and interpretation were performed by A.H., K.S., W.Z. and K.K. All authors have read and agreed to the published version of the manuscript.

Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

Data Availability Statement

No new data were created or analyzed in this study. Data sharing is not applicable to this article.

Acknowledgments

During the preparation of this manuscript, the authors used ChatGPT (OpenAI, GPT-4, 2025) for the purposes of improving the English language (grammar, style, and clarity). The authors have reviewed and edited the output and take full responsibility for the content of this publication.

Conflicts of Interest

The authors declare no conflicts of interest.

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Agronomy 15 02507 g001
Figure 1. Challenges and Limitations in Phage Application.
Figure 1. Challenges and Limitations in Phage Application.
Agronomy 15 02507 g001
Table 1. Overview of Bacterial Defence Mechanisms Against Bacteriophages.
Table 1. Overview of Bacterial Defence Mechanisms Against Bacteriophages.
Defence MechanismDescriptionExamplesTrade-Offs/Limitations
Inhibition of Capsule Production and LysogenizationBacteria inhibit capsule biosynthesis to survive under high phage pressure.Mutations inhibiting capsule biosynthesis; fine-tuning capsule production.High fitness cost due to the risk of prophage induction.
Inhibition of Phage AdsorptionPreventing phage attachment to the bacterial cell membrane.Biofilms, OMVs, surface receptor modifications, protein mimics.Increased susceptibility to antibiotics.
Blocking DNA InjectionThe Superinfection Exclusion (SIE) system prevents phage DNA injection.SIE proteins integrated into the bacterial membrane; interactions with type IV pili.Hinders long-term adaptation of viral populations.
Restriction–Modification SystemInternal defense systems activated to target the phage or eliminate the infected host.Sensor and effector systems.Protects remaining cellular population from viral particles.
Bacteriophage Exclusion (BREX)Allows phage DNA injection but prevents its replication through methylation modifications.Six-gene cassette in Bacillus cereus.Novel mechanism without cleaving phage DNA.
Defence Island System Associated with Restriction–Modification (DISARM)Prevents phage DNA replication through methylation modifications.Similar to BREX system.Does not cleave phage DNA.
CRISPR -Cas SystemsCaptures phage DNA segments and incorporates them into the bacterial genome as spacers to recognize and destroy phage DNA upon subsequent infections.Class 1 (types I, III, IV) and Class 2 (types II, V, VI) systems.Phages can evolve to evade the system; bacteria seldom acquire multiple spacers.
Abortive Infection (Abi)Induces controlled cell death or dormancy in the infected bacterial cell before the phage can complete its replication cycle.CBASS, Pycsar, Thoeris systems; RADA system.Preserves the surrounding microbial community; benefits related cells.
Toxin–Antitoxin SystemGenetic elements that inhibit host cell growth unless restrained by corresponding antitoxins.Type I-VIII systems; various toxins and antitoxins.Functions remain controversial; diverse mechanisms.
Bacteriophage Assembly InterferenceDisrupts the assembly of bacteriophages, preventing their successful replication.Phage-induced chromosomal islands (PICIs).Alters phage capsid size; depends on helper phages.
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Hoffmann, A.; Sadowska, K.; Zenelt, W.; Krawczyk, K. Bacteriophages as a Sustainable Tool for Plant Disease Management: Benefits and Challenges. Agronomy 2025, 15, 2507. https://doi.org/10.3390/agronomy15112507

AMA Style

Hoffmann A, Sadowska K, Zenelt W, Krawczyk K. Bacteriophages as a Sustainable Tool for Plant Disease Management: Benefits and Challenges. Agronomy. 2025; 15(11):2507. https://doi.org/10.3390/agronomy15112507

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Hoffmann, Anna, Katarzyna Sadowska, Weronika Zenelt, and Krzysztof Krawczyk. 2025. "Bacteriophages as a Sustainable Tool for Plant Disease Management: Benefits and Challenges" Agronomy 15, no. 11: 2507. https://doi.org/10.3390/agronomy15112507

APA Style

Hoffmann, A., Sadowska, K., Zenelt, W., & Krawczyk, K. (2025). Bacteriophages as a Sustainable Tool for Plant Disease Management: Benefits and Challenges. Agronomy, 15(11), 2507. https://doi.org/10.3390/agronomy15112507

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