Challenges of Antibiotic Resistance: Biofilms and Anti-Biofilm Agents

A special issue of Antibiotics (ISSN 2079-6382). This special issue belongs to the section "Antibiofilm Strategies".

Deadline for manuscript submissions: closed (31 May 2026) | Viewed by 4220

Special Issue Editors


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Guest Editor
Instituto Tecnológico del Valle del Yaqui, Bácum, Sonora, México
Interests: food safety; essential oils; agroindustrial byproducts; antibacterial and antibiofilm agents; quorum sensing
Special Issues, Collections and Topics in MDPI journals

E-Mail
Guest Editor
Departmento de Ingenierías, Instituto Tecnológico del Valle del Yaqui, Bácum, Sonora, Mexico
Interests: food safety; essential oils; bioactive compounds; terpenes; antibacterial and antibiofilm agents
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Antibiotic resistance is a global health crisis, as the rise in antibiotic-resistant bacteria has significantly increased the number of deaths each year because infections are becoming increasingly difficult to manage. This resistance is attributed to the overuse and misuse of antibiotics and microorganisms’ ability to form biofilms, which is a significant problem in several sectors, such as healthcare settings, the food industry, and environmental systems. Biofilms are complex communities of microorganisms embedded in a self-produced matrix of extracellular polymeric substances composed of carbohydrates, proteins, lipids, and extracellular DNA. This complex structure protects microorganisms from the action of antibiotics, as well as other environmental stresses. This resilience makes biofilms a critical factor in the growing challenge of antimicrobial resistance. In this sense, there is a need to find new antibiofilm agents that inhibit biofilm development and contribute to reducing bacterial antibiotic resistance.

This Special Issue invites researchers to publish studies regarding new antibiofilm agents (phytochemicals, synthetic drugs, nanoparticles, etc.) and their impacts on biofilms, virulence factors, and antibiotic resistance mechanisms.

Dr. María Melissa Gutiérrez-Pacheco
Dr. Luis Alberto Ortega-Ramirez
Guest Editors

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Keywords

  • antibiotic resistance
  • biofilms
  • quorum sensing
  • virulence factors
  • resistance mechanisms
  • antibiofilm agents
  • natural compounds
  • synthetic drugs

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Published Papers (4 papers)

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Research

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16 pages, 600 KB  
Article
Phenotypic Profiling of Biofilm Formation and Antibiotic Susceptibility in Poultry-Derived Listeria monocytogenes Isolates
by Evangelia A. Karamani, Eirini Kerousi, Margarita Adosidi, Georgios Vafeiadis, Ioannis S. Boziaris, Efstathios Giaouris and Foteini F. Parlapani
Antibiotics 2026, 15(6), 577; https://doi.org/10.3390/antibiotics15060577 - 5 Jun 2026
Viewed by 239
Abstract
Background/Objectives: Listeria monocytogenes is a critical foodborne pathogen, with poultry products serving as a potential reservoir. Its ability to form biofilms may aid in its persistence on processing equipment and food-contact surfaces, while antibiotic resistance complicates efforts to control and treat infections. [...] Read more.
Background/Objectives: Listeria monocytogenes is a critical foodborne pathogen, with poultry products serving as a potential reservoir. Its ability to form biofilms may aid in its persistence on processing equipment and food-contact surfaces, while antibiotic resistance complicates efforts to control and treat infections. This study aimed to characterize, in parallel, the biofilm-forming capacity and antibiotic susceptibility of a large collection of poultry-derived L. monocytogenes isolates (n = 93) to better understand their potential for persistence and to clarify how the biofilm phenotype may relate to the bacterial antibiotic response and to inform risk assessment and targeted control strategies along poultry processing and supply chains. Methods: Biofilms were evaluated on polystyrene microtiter plates at 12 and 30 °C in a nutrient-rich laboratory medium. Susceptibility to eight clinically and food-relevant antibiotics was tested using disk diffusion and interpreted according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints when available. Results: At 30 °C for 48 h, 69.9% of isolates were classified as weak biofilm formers and 30.1% as non-biofilm formers, whereas at 12 °C for 120 h, 55.9% were weak, 16.1% moderate, and 28.0% non-biofilm formers, with no strong biofilm producers identified under either condition. Overall, the isolates remained largely susceptible to ampicillin, penicillin G, vancomycin, tetracycline, and chloramphenicol, with 87.3% of inhibition zones across all drugs falling within the 20–29 mm and 30–39 mm categories, while small subpopulations showed reduced susceptibility or resistance to trimethoprim–sulphamethoxazole (TMP-SMX) and, particularly, erythromycin and streptomycin. No consistent correlation was found between biofilm-forming ability and antibiotic susceptibility, indicating that these phenotypic traits are largely independent in this collection. Conclusions: These findings reveal that poultry-derived L. monocytogenes isolates can form weak to moderate biofilms under the tested monoculture conditions while generally maintaining susceptibility to first-line antibiotics. However, the development of macrolide- and aminoglycoside-resistant subpopulations, along with the potential for increased colonization within complex multispecies biofilms in real processing environments, emphasizes the importance of ongoing integrated surveillance across animal food systems. Full article
(This article belongs to the Special Issue Challenges of Antibiotic Resistance: Biofilms and Anti-Biofilm Agents)
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21 pages, 4680 KB  
Article
Deep Eutectic Solvent-Based Emulsion Containing Piper betle L. Extract and Hydroxychavicol Prevent Biofilm Development and Surface Adhesion of Avian Pathogenic Escherichia coli on Stored Chicken Meat
by Kunchaphorn Ratchasong, Phirabhat Saengsawang, Gorawit Yusakul, Krittika Kabploy, Hemanth Kumar Lakhanapuram, Aliakbur Harudeen, Phitchayapak Wintachai, Thotsapol Thomrongsuwannakij, Ozioma Forstinus Nwabor and Watcharapong Mitsuwan
Antibiotics 2026, 15(4), 328; https://doi.org/10.3390/antibiotics15040328 - 24 Mar 2026
Viewed by 639
Abstract
Background: Avian pathogenic Escherichia coli (APEC) contributes substantially to colibacillosis outbreaks in chickens. Because APEC cells readily attach to surfaces and develop biofilms, they pose a notable hazard to poultry production and food safety. This study investigated the antibiofilm and anti-adhesion activities of [...] Read more.
Background: Avian pathogenic Escherichia coli (APEC) contributes substantially to colibacillosis outbreaks in chickens. Because APEC cells readily attach to surfaces and develop biofilms, they pose a notable hazard to poultry production and food safety. This study investigated the antibiofilm and anti-adhesion activities of deep eutectic solvent-based emulsion containing Piper betle L. extract (DEPE) and hydroxychavicol, a pure compound isolated from P. betle leaves against APEC. Methods: Antibiofilm and anti-adhesion activities of DEPE and hydroxychavicol against APEC were investigated. Molecular docking and dynamics simulation of DEPE and hydroxychavicol was conducted. In addition, anti-adhesion activity of DEPE on chicken meat during storage was evaluated. Results: DEPE and hydroxychavicol significantly inhibited biofilm formation at sub-MIC, with DEPE achieving up to 80% inhibition and hydroxychavicol up to 69%. At 8 × MIC, DEPE and hydroxychavicol diminished the viability of both early and established biofilms. Furthermore, DEPE and hydroxychavicol reduced APEC adhesion on the surface as observed by SEM. In silico analyses demonstrated the stable binding of hydroxychavicol to adhesion-related proteins, particularly EcpA and FimH, suggesting a possible mechanism for its anti-adhesion activity. At day 5, DEPE at 4 × MIC significantly reduced 63% bacterial adhesion to chicken meat surfaces during storage, while maintaining the meat’s color. Conclusions: These findings indicate that DEPE and hydroxychavicol are promising candidates for limiting APEC biofilm formation and surface attachment and may serve as alternative antibacterial agents in poultry-related food safety applications. Full article
(This article belongs to the Special Issue Challenges of Antibiotic Resistance: Biofilms and Anti-Biofilm Agents)
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23 pages, 3957 KB  
Article
Pathogen-Specific Actinium-225 and Lutetium-177 Labeled Antibodies for Treatment of Biofilm-Associated Implant Infections: Initial In Vivo Proof-of-Concept
by F. Ruben H. A. Nurmohamed, Kevin J. H. Allen, Mackenzie E. Malo, Connor Frank, J. Fred F. Hooning van Duvenbode, Berend van der Wildt, Alex J. Poot, Marnix G. E. H. Lam, Jos A. G. van Strijp, Peter G. J. Nikkels, H. Charles Vogely, Harrie Weinans, Ekaterina Dadachova and Bart C. H. van der Wal
Antibiotics 2025, 14(12), 1283; https://doi.org/10.3390/antibiotics14121283 - 18 Dec 2025
Cited by 2 | Viewed by 814
Abstract
Background: the primary challenge with implant infections is the formation of biofilm, which harbors dormant bacteria that reduce the effectiveness of antibiotics and amplify antibiotic resistance, exacerbating the global antimicrobial resistance crisis. A potential novel treatment strategy is radioimmunotherapy, which uses antibodies linked [...] Read more.
Background: the primary challenge with implant infections is the formation of biofilm, which harbors dormant bacteria that reduce the effectiveness of antibiotics and amplify antibiotic resistance, exacerbating the global antimicrobial resistance crisis. A potential novel treatment strategy is radioimmunotherapy, which uses antibodies linked to radioisotopes to deliver targeted radiation to the bacteria and biofilm. We describe the first in vivo use of targeted radiation therapy, employing Actinium-225 (α-radiation) and Lutetium-177 (β-radiation) labeled antibodies to treat a Staphylococcus aureus biofilm-associated intramedullary implant infection. Untargeted radiation in the form of unbound radionuclide treatment was also evaluated. Methods: to assess therapeutic efficacy, bacterial counts were performed on implant and surrounding bone after seven days of follow-up. Biodistribution was evaluated using SPECT/CT and ex vivo gamma counting. Results: radioimmunotherapy using an antibody against wall teichoic acid which was labeled with Actinium-225 and Lutetium-177 achieved bacterial reductions between 45% and 93% on the implant and surrounding bone. Surprisingly, a similar antimicrobial effect was observed with unbound Actinium-225 treatment reducing the bacterial load by 80% on the implant and 98% in the surrounding bone. Indications of maximum tolerated dose (MTD) with Lutetium-177 labeled antibodies were observed through hepatic and renal function evaluations. Conclusions: These results should be interpreted in the context of the study’s constraints, particularly the limited animal sample size. Nonetheless, the results suggest that in vivo applied radiation may help reduce a biofilm-associated infection at the implant site as well as in the surrounding bone. These findings encourage further investigation into the use of targeted and non-targeted radiation, potentially combined with antibiotics, to develop effective strategies for eradicating biofilm-associated implant infections. Full article
(This article belongs to the Special Issue Challenges of Antibiotic Resistance: Biofilms and Anti-Biofilm Agents)
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Review

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31 pages, 2995 KB  
Review
Joining Forces Against Antibiotic Resistance in Aquaculture: The Synergism Between Natural Compounds and Antibiotics
by María Melissa Gutiérrez-Pacheco, Martina Hilda Gracia-Valenzuela, Luis Alberto Ortega-Ramirez, Francisco Javier Vázquez-Armenta, Juan Manuel Leyva, Jesús Fernando Ayala-Zavala and Andrés Francisco Chávez-Almanza
Antibiotics 2026, 15(1), 95; https://doi.org/10.3390/antibiotics15010095 - 16 Jan 2026
Cited by 2 | Viewed by 1499
Abstract
The intensification of aquaculture practices has been accompanied by an increased incidence of bacterial diseases, leading to a greater reliance on antibiotics for disease control. Consequently, the widespread and often indiscriminate use of these compounds has contributed to the emergence and dissemination of [...] Read more.
The intensification of aquaculture practices has been accompanied by an increased incidence of bacterial diseases, leading to a greater reliance on antibiotics for disease control. Consequently, the widespread and often indiscriminate use of these compounds has contributed to the emergence and dissemination of antibiotic-resistant bacteria within aquaculture systems, posing a serious threat to animal health, environmental sustainability, and public health. In this regard, research efforts have focused on developing alternative strategies to reduce antibiotic use. Natural compounds have gained particular attention due to their well-documented antimicrobial and antibiofilm activities. In this context, the combined application of antibiotics and natural compounds has emerged as a promising approach to enhance antimicrobial efficacy while potentially mitigating the development of resistance. This review synthesizes the current knowledge on antibiotic resistance in aquaculture, highlights the role of biofilm formation as a key resistance mechanism, and critically examines the potential of antibiotic–natural compound combinations against major aquaculture pathogens, with particular emphasis on bacterial growth inhibition, biofilm disruption, and virulence attenuation. Collectively, the evidence discussed underscores the potential of synergistic strategies as a sustainable tool for improving disease management in aquaculture while supporting efforts to limit antibiotic resistance. Full article
(This article belongs to the Special Issue Challenges of Antibiotic Resistance: Biofilms and Anti-Biofilm Agents)
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