{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T10:26:25Z","timestamp":1787307985684,"version":"build-2736575974"},"reference-count":60,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Albert Szent-Gy\u00f6rgyi Grant of the University of Szeged"},{"id":[{"id":"https:\/\/ror.org\/01pnej532","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background\/Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) is a major therapeutic challenge due to its extensive antibiotic resistance. This study examined how bacteriophage exposure affects the genome, proteome and antibiotic susceptibility of a clinical MRSA isolate. Methods: The MRSA isolate was exposed to the PYOFAG bacteriophage cocktail, and small colony variants (SCVs) of the surviving bacteria were compared with the untreated parental strain by phenotypic testing, whole-genome sequencing, comparative proteomics, and transmission electron microscopy. Results: Phage exposure induced marked remodeling in MRSA, including altered growth, colony morphology, and increased susceptibility to various antibiotics, especially \u03b2-lactams and aminoglycosides. Genomic analysis identified multiple mutations and the loss of two genomic regions, including changes in tarS, a gene linked to wall teichoic acid glycosylation, phage adsorption, and \u03b2-lactam resistance. Proteomic analysis revealed broad changes in metabolic, stress-response, and cell-envelope-associated pathways. Transmission electron microscopy showed a significant reduction in cell wall thickness after phage treatment. Conclusions: Bacteriophage exposure drives phenotypic and molecular adaptation in MRSA and may create evolutionary trade-offs that weaken resistance mechanisms. These findings support the potential of bacteriophages as both direct antibacterial agents and modulators of antibiotic susceptibility.<\/jats:p>","DOI":"10.3390\/antibiotics15080800","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T09:06:41Z","timestamp":1787044001000},"page":"800","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Bacteriophage Challenge Drives Genomic and Proteomic Remodeling and Alters Antibiotic Resistance in a Methicillin-Resistant Staphylococcus aureus"],"prefix":"10.3390","volume":"15","author":[{"given":"Ot\u00edlia","family":"V\u00e1g\u00f3","sequence":"first","affiliation":[{"name":"P\u00e1ndy K\u00e1lm\u00e1n County Hospital, Semmelweis Str. 1, H-5700 Gyula, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kriszti\u00e1n","family":"Laczi","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Microbiology, University of Szeged, K\u00f6z\u00e9p fasor 52, H-6726 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5268-6134","authenticated-orcid":false,"given":"L\u00e1szl\u00f3","family":"Orosz","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Albert Szent-Gy\u00f6rgyi Health Center and Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, Semmelweis Str. 6, H-6725 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-1613-7436","authenticated-orcid":false,"given":"Georgina","family":"Horv\u00e1th","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Albert Szent-Gy\u00f6rgyi Health Center and Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, Semmelweis Str. 6, H-6725 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9926-0918","authenticated-orcid":false,"given":"K\u00e1roly P\u00e9ter","family":"S\u00e1rv\u00e1ri","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Albert Szent-Gy\u00f6rgyi Health Center and Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, Semmelweis Str. 6, H-6725 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4482-0740","authenticated-orcid":false,"given":"Di\u00e1na","family":"Szab\u00f3","sequence":"additional","affiliation":[{"name":"Department of Oto-Rhino-Laryngology and Head & Neck Surgery, University of Szeged, Tisza Lajos Str. 111, H-6724 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regina","family":"Csord\u00e1s","sequence":"additional","affiliation":[{"name":"Department of Medical Chemistry, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, D\u00f3m Sq. 8, H-6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8278-8038","authenticated-orcid":false,"given":"Zolt\u00e1n","family":"Szab\u00f3","sequence":"additional","affiliation":[{"name":"Department of Medical Chemistry, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, D\u00f3m Sq. 8, H-6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7915-4437","authenticated-orcid":false,"given":"Caleb","family":"Ardizzone","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Department of Medicine, Indiana University School of Medicine, 635 Barnhill Drive, MS 258, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9854-7340","authenticated-orcid":false,"given":"Titanilla","family":"Sz\u00f6gi","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University of Szeged, \u00c1llom\u00e1s Str. 1, H-6725 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1300-2374","authenticated-orcid":false,"given":"Katalin","family":"Buri\u00e1n","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Albert Szent-Gy\u00f6rgyi Health Center and Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, Semmelweis Str. 6, H-6725 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dezs\u0151 P\u00e9ter","family":"Virok","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Albert Szent-Gy\u00f6rgyi Health Center and Albert Szent-Gy\u00f6rgyi Medical 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