{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:32:15Z","timestamp":1787027535819,"version":"build-2736575974"},"reference-count":48,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T00:00:00Z","timestamp":1753315200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"BIOTEGANIA","award":["PLEC2023-010275"],"award-info":[{"award-number":["PLEC2023-010275"]}]},{"name":"BIOTEGANIA","award":["MCIN\/AEI\/10.13039\/501100011033"],"award-info":[{"award-number":["MCIN\/AEI\/10.13039\/501100011033"]}]},{"name":"BIOTEGANIA","award":["MIG-20232001"],"award-info":[{"award-number":["MIG-20232001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background\/Objectives: As bacteriophage-based strategies to control bacterial pathogens continue to gain momentum, phage therapy is increasingly being explored across various fields. In the poultry industry, efforts to minimize the public health impact of Salmonella have spurred growing interest in phage applications, particularly as prophylactic and disinfecting agents. Although the disinfecting potential of bacteriophages has been recognized, in-depth studies examining their efficacy under varying environmental conditions remain limited. This study focused on evaluating the effectiveness of bacteriophages as disinfecting agents against biofilm-forming Salmonella Infantis under different environments. Methods: A comprehensive screening of biofilm-producing strains was conducted using Congo Red Agar and 96-well plate assays. Two strains with distinct biofilm-forming capacities were selected for further analysis under different environmental conditions: aerobic and microaerobic atmospheres at both 25 \u00b0C and 37 \u00b0C. The resulting biofilms were then treated with four phage preparations: three individual phages and one phage cocktail. Biofilm reduction was assessed by measuring optical density and CFU\/well. Additionally, scanning electron microscopy was used to visualize both untreated and phage-treated biofilms. Results: The results demonstrated that all S. Infantis strains were capable of forming biofilms (21\/21). All three phage candidates exhibited biofilm-disrupting activity and were able to lyse biofilm-embedded Salmonella cells. Notably, the lytic efficacy of the phages varied depending on environmental conditions, highlighting the importance of thorough phage characterization prior to application. Conclusions: These findings underscore that the effectiveness of bacteriophages as surface disinfectants can be significantly compromised if inappropriate phages are used, especially in the presence of biofilms.<\/jats:p>","DOI":"10.3390\/antibiotics14080744","type":"journal-article","created":{"date-parts":[[2025,7,24]],"date-time":"2025-07-24T11:58:53Z","timestamp":1753358333000},"page":"744","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["In Vitro Insights into the Anti-Biofilm Potential of Salmonella Infantis Phages"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3431-218X","authenticated-orcid":false,"given":"Jan","family":"Torres-Boncompte","sequence":"first","affiliation":[{"name":"Centro de Calidad Av\u00edcola y Alimentaci\u00f3n Animal de la Comunidad Valenciana (CECAV), 12539 Castell\u00f3n, Spain"},{"name":"Food & Health Lab, Institute of Materials Science, University of Valencia, 46980 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9885-0917","authenticated-orcid":false,"given":"Mar\u00eda","family":"Sanz-Zapata","sequence":"additional","affiliation":[{"name":"Centro de Calidad Av\u00edcola y Alimentaci\u00f3n Animal de la Comunidad Valenciana (CECAV), 12539 Castell\u00f3n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7939-3899","authenticated-orcid":false,"given":"Josep","family":"Garcia-Llorens","sequence":"additional","affiliation":[{"name":"Centro de Calidad Av\u00edcola y Alimentaci\u00f3n Animal de la Comunidad Valenciana (CECAV), 12539 Castell\u00f3n, Spain"},{"name":"Food & Health Lab, Institute of Materials Science, University of Valencia, 46980 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2846-1311","authenticated-orcid":false,"given":"Jos\u00e9 M.","family":"Soriano","sequence":"additional","affiliation":[{"name":"Food & Health Lab, Institute of Materials Science, University of Valencia, 46980 Valencia, Spain"},{"name":"Joint Research Unit on Endocrinology, Nutrition and Clinical Dietetics, University of Valencia-Health Research Institute La Fe, 46026 Valencia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8298-102X","authenticated-orcid":false,"given":"Pablo","family":"Catal\u00e1-Gregori","sequence":"additional","affiliation":[{"name":"Centro de Calidad Av\u00edcola y Alimentaci\u00f3n Animal de la Comunidad Valenciana (CECAV), 12539 Castell\u00f3n, Spain"},{"name":"Departamento de Producci\u00f3n y Sanidad Animal, Salud P\u00fablica Veterinaria y Ciencia y Tecnolog\u00eda de los Alimentos, Instituto de Ciencias Biom\u00e9dicas, Facultad de Veterinaria, Universidad Cardenal Herrera-CEU, CEU Universities, 46113 Moncada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2354-9800","authenticated-orcid":false,"given":"Sandra","family":"Sevilla-Navarro","sequence":"additional","affiliation":[{"name":"Centro de Calidad Av\u00edcola y Alimentaci\u00f3n Animal de la Comunidad Valenciana (CECAV), 12539 Castell\u00f3n, Spain"},{"name":"Departamento de Producci\u00f3n y Sanidad Animal, Salud P\u00fablica Veterinaria y Ciencia y Tecnolog\u00eda de los Alimentos, Instituto de Ciencias Biom\u00e9dicas, Facultad de Veterinaria, Universidad Cardenal Herrera-CEU, CEU Universities, 46113 Moncada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2229937","DOI":"10.1080\/19490976.2023.2229937","article-title":"Better together\u2013Salmonella biofilm-associated antibiotic resistance","volume":"15","author":"Aleksandrowicz","year":"2023","journal-title":"Gut Microbes"},{"key":"ref_2","first-page":"166","article-title":"Salmonella enterica serovar enteritidis biofilm lifestyle induces lower pathogenicity and reduces inflammatory response in a murine model compared to planktonic bacteria","volume":"54","author":"Giacomodonato","year":"2022","journal-title":"Rev. Argent. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/B978-0-12-378612-8.00112-8","article-title":"Bacteria: Salmonella non-typhi","volume":"1","author":"Ethelberg","year":"2014","journal-title":"Encycl. Food Saf."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Keerthirathne, T.P., Ross, K., Fallowfield, H., and Whiley, H. (2016). A review of temperature, pH, and other factors that influence the survival of Salmonella in mayonnaise and other raw egg products. Pathogens, 5.","DOI":"10.3390\/pathogens5040063"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"EFSA & ECDC (2024). The European Union One Health 2023 Zoonoses Report. EFSA J., 22, e9106.","DOI":"10.2903\/j.efsa.2024.9106"},{"key":"ref_6","unstructured":"World Health Organization (2025, July 22). Salmonella (Non-Typhoidal). Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/salmonella-(non-typhoidal)."},{"key":"ref_7","unstructured":"Grimont, P.A.D., and Weill, F.-X. (2007). Antigenic Formulae of the Salmonella Serovars, Institut Pasteur."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Alvarez, D.M., Barr\u00f3n-Montenegro, R., Conejeros, J., Rivera, D., Undurraga, E.A., and Moreno-Switt, A.I. (2023). A review of the global emergence of multidrug-resistant Salmonella enterica subsp. enterica serovar Infantis. Int. J. Food Microbiol., 403.","DOI":"10.1016\/j.ijfoodmicro.2023.110297"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e02481-22","DOI":"10.1128\/spectrum.02481-22","article-title":"Clonal spread of pESI-positive multidrug-resistant ST32 Salmonella enterica serovar Infantis isolates among broilers and humans in Slovenia","volume":"10","author":"Ocepek","year":"2022","journal-title":"Microbiol. Spectr."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Carrascosa, C., Raheem, D., Ramos, F., Saraiva, A., and Raposo, A. (2021). Microbial biofilms in the food industry\u2014A comprehensive review. Int. J. Environ. Res. Public Health, 18.","DOI":"10.3390\/ijerph18042014"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Harrell, J.E., Hahn, M.M., D\u2019Souza, S.J., Vasicek, E.M., Sandala, J.L., Gunn, J.S., and McLachlan, J.B. (2021). Salmonella biofilm formation, chronic infection, and immunity within the intestine and hepatobiliary tract. Front. Cell Infect. Microbiol., 10.","DOI":"10.3389\/fcimb.2020.624622"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Yin, W., Wang, Y., Liu, L., and He, J. (2019). Biofilms: The microbial \u201cProtective Clothing\u201d in extreme environments. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20143423"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/s13756-019-0533-3","article-title":"Antibiotics versus biofilm: An emerging battleground in microbial communities","volume":"8","author":"Sharma","year":"2019","journal-title":"Antimicrob. Resist. Infect. Control"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Gali\u00e9, S., Garc\u00eda-Guti\u00e9rrez, C., Migu\u00e9lez, E.M., Villar, C.J., and Lomb\u00f3, F. (2018). Biofilms in the food industry: Health aspects and control methods. Front. Microbiol., 9.","DOI":"10.3389\/fmicb.2018.00898"},{"key":"ref_15","unstructured":"Sherman, M. (2025, June 13). Bacteriophages: Beyond Antibiotics. Available online: https:\/\/www.uspharmacist.com\/article\/bacteriophages-beyond-antibiotics."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Hyman, P. (2019). Phages for Phage therapy: Isolation, characterization, and host range breadth. Pharmaceuticals, 12.","DOI":"10.3390\/ph12010035"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Subramanian, A. (2024). Emerging roles of bacteriophage-based therapeutics in combating antibiotic resistance. Front. Microbiol., 15.","DOI":"10.3389\/fmicb.2024.1384164"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"216","DOI":"10.3382\/ps.2013-03360","article-title":"Bacteriophage-induced reduction in Salmonella Enteritidis counts in the crop of broiler chickens undergoing preslaughter feed withdrawal","volume":"93","author":"Donato","year":"2014","journal-title":"Poult. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1002\/jobm.201800412","article-title":"Bacteriophages: An overview of the control strategies against multiple bacterial infections in different fields","volume":"59","author":"Jamal","year":"2019","journal-title":"J. Basic. Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.apsb.2023.08.017","article-title":"Translating bacteriophage-derived depolymerases into antibacterial therapeutics: Challenges and prospects","volume":"14","author":"Wang","year":"2023","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Korzeniowski, P., \u015aliwka, P., Kuczkowski, M., Mi\u0161i\u0107, D., Milcarz, A., and Ku\u017ami\u0144ska-Bajor, M. (2022). Bacteriophage cocktail can effectively control Salmonella biofilm in poultry housing. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.901770"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1128\/AEM.03109-13","article-title":"Commonly used disinfectants fail to eradicate Salmonella enterica biofilms from food contact surface materials","volume":"80","author":"Corcoran","year":"2014","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"112700","DOI":"10.1016\/j.lwt.2021.112700","article-title":"Comparative study of Salmonella Typhimurium biofilms and their resistance depending on cellulose secretion and maturation temperatures","volume":"154","author":"Kim","year":"2022","journal-title":"LWT"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"906","DOI":"10.4315\/0362-028X-68.5.906","article-title":"Biofilm formation, cellulose production, and curli biosynthesis by Salmonella originating from produce, animal, and clinical sources","volume":"68","author":"Solomon","year":"2005","journal-title":"J. Food Prot."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1046\/j.1365-2958.2002.02802.x","article-title":"Genetic analysis of Salmonella Enteritidis biofilm formation: Critical role of cellulose","volume":"43","author":"Solano","year":"2002","journal-title":"Mol. Microbiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1007\/s00284-021-02373-4","article-title":"Biofilm formation by Salmonella enterica strains","volume":"78","author":"Shatila","year":"2021","journal-title":"Curr. Microbiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1080\/08927014.2016.1191068","article-title":"Salmonella enterica isolates from layer farm environments are able to form biofilm on eggshell surfaces","volume":"32","author":"Pande","year":"2016","journal-title":"Biofouling"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Bezek, K., Avber\u0161ek, J., Zorman Rojs, O., and Barli\u010d-Maganja, D. (2023). Antimicrobial and antibiofilm effect of commonly used disinfectants on Salmonella Infantis isolates. Microorganisms, 11.","DOI":"10.3390\/microorganisms11020301"},{"key":"ref_29","unstructured":"(2025, June 17). Aviagen Ross Broilers Pocketguide. Available online: https:\/\/aviagen.com\/assets\/Tech_Center\/Ross_Broiler\/Aviagen-ROSS-Broiler-PocketGuide-EN.pdf."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3392","DOI":"10.3382\/ps\/pex124","article-title":"Bacteriophage use to control Salmonella biofilm on surfaces present in chicken slaughterhouses","volume":"96","author":"Pereira","year":"2017","journal-title":"Poult. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1116","DOI":"10.4315\/0362-028X-64.8.1116","article-title":"Examination of bacteriophage as a biocontrol method for Salmonella on fresh-cut fruit: A model study","volume":"64","author":"Leverentz","year":"2001","journal-title":"J. Food Prot."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Sevilla-Navarro, S., Torres-Boncompte, J., Garcia-Llorens, J., Bernab\u00e9u-Gimeno, M., Domingo-Calap, P., and Catal\u00e1-Gregori, P. (2024). Fighting Salmonella Infantis: Bacteriophage-driven cleaning and disinfection strategies for broiler farms. Front. Microbiol., 15.","DOI":"10.3389\/fmicb.2024.1401479"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Torres-Boncompte, J., G\u00f3mez-Cano, I.S., Garcia-Llorens, J., Soriano, J.M., Catal\u00e1-Gregori, P., and Sevilla-Navarro, S. (2025). Characterization and therapeutic potential of newly isolated bacteriophages targeting the most common Salmonella serovars in Europe. Sci. Rep., 15.","DOI":"10.1038\/s41598-025-95398-9"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Molina, F., Simancas, A., Ram\u00edrez, M., Tabla, R., Roa, I., and Rebollo, J.E. (2021). A new pipeline for designing phage cocktails based on phage-bacteria infection networks. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.564532"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"D\u00edaz-Gali\u00e1n, M.V., Vega-Rodr\u00edguez, M.A., and Molina, F. (2022). PhageCocktail: An R package to design phage cocktails from experimental phage-bacteria infection networks. Comput. Methods Programs Biomed., 221.","DOI":"10.1016\/j.cmpb.2022.106865"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"104372","DOI":"10.1016\/j.isci.2022.104372","article-title":"Genomic characterization of lytic bacteriophages targeting genetically diverse Pseudomonas aeruginosa clinical isolates","volume":"25","author":"Nordstrom","year":"2022","journal-title":"iScience"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Haeusser, D.P., Hoashi, M., Weaver, A., Brown, N., Pan, J., Sawitzke, J.A., Thomason, L.C., Court, D.L., and Margolin, W. (2014). The kil peptide of bacteriophage \u03bb blocks Escherichia coli cytokinesis via ZipA-dependent inhibition of FtsZ assembly. PLoS Genet., 10.","DOI":"10.1371\/journal.pgen.1004217"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Mohamed, A., Taha, O., El-Sherif, H.M., Connerton, P.L., Hooton, S.P.T., Bassim, N.D., Connerton, I.F., and El-Shibiny, A. (2020). Bacteriophage ZCSE2 is a potent antimicrobial against Salmonella enterica serovars: Ultrastructure, genomics and efficacy. Viruses, 12.","DOI":"10.3390\/v12040424"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1146\/annurev-virology-091919-074222","article-title":"Understanding the complex phage-host interactions in biofilm communities","volume":"8","author":"Pires","year":"2021","journal-title":"Annu. Rev. Virol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"197759","DOI":"10.1016\/j.virusres.2019.197759","article-title":"Resistance mechanisms adopted by a Salmonella Typhimurium mutant against bacteriophage","volume":"273","author":"Wang","year":"2019","journal-title":"Virus Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e01872-24","DOI":"10.1128\/jvi.01872-24","article-title":"Quorum sensing inhibits phage infection by regulating biofilm formation of P. aeruginosa PAO1","volume":"99","author":"Cao","year":"2025","journal-title":"J. Virol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Fister, S., Robben, C., Witte, A.K., Schoder, D., Wagner, M., and Rossmanith, P. (2016). Influence of environmental factors on phage-bacteria interaction and on the efficacy and infectivity of phage P100. Front. Microbiol., 7.","DOI":"10.3389\/fmicb.2016.01152"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Sevilla-Navarro, S., Otero, J., L\u00f3pez-P\u00e9rez, J., Torres-Boncompte, J., Prucha, T., De Gussem, M., Silva, D., Burgan, J., Catal\u00e1-Gregori, P., and Cort\u00e9s, P. (2024). Limited emergence of Salmonella enterica serovar Infantis variants with reduced phage susceptibility in PhagoVet-treated broilers. Animals, 14.","DOI":"10.3390\/ani14162352"},{"key":"ref_44","first-page":"2287","article-title":"A 96 well microtiter plate-based method for monitoring formation and antifungal susceptibility testing of Candida albicans biofilms","volume":"44","author":"Pierce","year":"2010","journal-title":"J. Vis. Exp."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/s10123-022-00294-1","article-title":"Antibiofilm Activity of a lytic Salmonella phage on different Salmonella enterica serovars isolated from broiler farms","volume":"26","author":"Hosny","year":"2023","journal-title":"Int. Microbiol."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Thames, H.T., Pokhrel, D., Willis, E., Rivers, O., Dinh, T.T.N., Zhang, L., Schilling, M.W., Ramachandran, R., White, S., and Sukumaran, A.T. (2023). Salmonella biofilm formation under fluidic shear stress on different surface materials. Foods, 12.","DOI":"10.3390\/foods12091918"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Guill\u00edn, Y., C\u00e1ceres, M., Torres, R., Stashenko, E., and Ortiz, C. (2021). Effect of essential oils on the inhibition of biofilm and quorum sensing in Salmonella Enteritidis 13076 and Salmonella Typhimurium 14028. Antibiotics, 10.","DOI":"10.3390\/antibiotics10101191"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/nmeth.2089","article-title":"NIH Image to ImageJ: 25 years of image analysis","volume":"9","author":"Schneider","year":"2012","journal-title":"Nat. Methods"}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/14\/8\/744\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:15:19Z","timestamp":1760033719000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/14\/8\/744"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,24]]},"references-count":48,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8]]}},"alternative-id":["antibiotics14080744"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics14080744","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,24]]}}}