{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T16:32:24Z","timestamp":1790440344349,"version":"4.1.0"},"reference-count":87,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2022,11,9]],"date-time":"2022-11-09T00:00:00Z","timestamp":1667952000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Vice-Chancellor of Research and Technology of Hamadan University of Medical Sciences, Hamadan, Iran","award":["9809056605"],"award-info":[{"award-number":["9809056605"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>\n                    <jats:italic>Staphylococcus epidermis<\/jats:italic>\n                    is one of the most frequent causes of device-associated infections due to biofilm formation. Current reports noted that subinhibitory concentrations of antibiotics induce biofilm production in some bacteria. Accordingly, we evaluated the effect of exposure of different subinhibitory concentrations of cloxacillin, cefazolin, clindamycin, and vancomycin on the biofilm formation of methicillin-resistant\n                    <jats:italic>S<\/jats:italic>\n                    .\n                    <jats:italic>epidermidis<\/jats:italic>\n                    (MRSE). Antimicrobial susceptibility testing and minimum inhibitory\/bactericidal concentration of antimicrobial agents were determined. MRSE isolates were selected, and their biofilm formation ability was evaluated. The effect of subinhibitory concentrations of cloxacillin, cefazolin, clindamycin, and vancomycin, antibiotics selected among common choices in the clinic, on MRSE biofilm formation was determined by the microtitre method. Besides, the effect of subinhibitory concentrations of cloxacillin, cefazolin, clindamycin, and vancomycin on the expression of the biofilm-associated genes\n                    <jats:italic>icaA<\/jats:italic>\n                    and\n                    <jats:italic>atlE<\/jats:italic>\n                    was evaluated by Reverse-transcription quantitative real-time polymerase chain reaction (RT-qPCR). Antimicrobial susceptibility patterns of MRSE strains showed a high level of resistance as follows: 80%, 53.3%, 33.3%, 33.3%, and 26.6%, for erythromycin, trimethoprim-sulfamethoxazole, tetracycline, clindamycin, and gentamicin, respectively. Besides, 73.3% of\n                    <jats:italic>S<\/jats:italic>\n                    .\n                    <jats:italic>epidermidis<\/jats:italic>\n                    strains were Multidrug-resistant (MDR). Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values were in the range of 0.5 to512 \u03bcg\/mL and 1 to1024 \u03bcg\/mL for cloxacillin, 0.125 to256 \u03bcg\/mL and 1 to512 \u03bcg\/mL for cefazolin, 0.125 to64 \u03bcg\/mL and 4 to&gt;1024 \u03bcg\/mL for clindamycin, and 2 to32 \u03bcg\/mL and 4 to32 \u03bcg\/mL for vancomycin, respectively. The findings showed that subinhibitory concentrations of cloxacillin, cefazolin, and clindamycin induce biofilm production in MRSE strains. In particular, the OD values of strains were in the range of 0.09\u20130.95, 0.05\u20130.86, and 0.06\u20131 toward cloxacillin, cefazolin, and clindamycin, respectively. On the other hand, exposure to subinhibitory vancomycin concentrations did not increase the biofilm formation in MRSE strains. The findings also demonstrated that sub-MIC of antibiotics up-regulated biofilm-associated genes. In particular,\n                    <jats:italic>atlE<\/jats:italic>\n                    and\n                    <jats:italic>icaA<\/jats:italic>\n                    were up-regulated 0.062 to 1.16 and 0.078 to 1.48 folds, respectively, for cloxacillin, 0.11 to 0.8, and 0.1 to 1.3 folds for cefazolin, 0.18 to 0.98, and 0.19 to 1.4 folds, respectively, for clindamycin. In contrast, the results showed that sub-MIC of vancomycin did not increase the biofilm-associated genes. These findings overall show that exposure to sub-MIC of traditional antibiotics can cause biofilm induction in MRSE, thereby increasing the survival and persistence on various surfaces that worsen the condition of comorbid infections.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0277287","type":"journal-article","created":{"date-parts":[[2022,11,9]],"date-time":"2022-11-09T13:49:09Z","timestamp":1668001749000},"page":"e0277287","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":38,"title":["The issue beyond resistance: Methicillin-resistant Staphylococcus epidermidis biofilm formation is induced by subinhibitory concentrations of cloxacillin, cefazolin, and clindamycin"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4148-6495","authenticated-orcid":true,"given":"Rasoul","family":"Mirzaei","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rasoul","family":"Yousefimashouf","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Reza","family":"Arabestani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iraj","family":"Sedighi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Yousef","family":"Alikhani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,11,9]]},"reference":[{"key":"pone.0277287.ref001","doi-asserted-by":"crossref","first-page":"xtaa004","DOI":"10.1093\/femsmc\/xtaa004","article-title":"Issues beyond resistance: inadequate antibiotic therapy and bacterial hypervirulence","volume":"1","author":"LW Goneau","year":"2020","journal-title":"FEMS Microbes"},{"key":"pone.0277287.ref002","article-title":"WHO warns against \u2019post-antibiotic\u2019 era","author":"S Reardon","year":"2014","journal-title":"Nature"},{"key":"pone.0277287.ref003","doi-asserted-by":"crossref","first-page":"2097","DOI":"10.1002\/iub.2356","article-title":"Bacterial co-infections with SARS-CoV-2","volume":"72","author":"R Mirzaei","year":"2020","journal-title":"IUBMB 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