{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T19:30:53Z","timestamp":1792092653899,"version":"4.4.0"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,11,18]],"date-time":"2023-11-18T00:00:00Z","timestamp":1700265600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,11,18]],"date-time":"2023-11-18T00:00:00Z","timestamp":1700265600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100003789","name":"Helwan University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003789","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Braz J Microbiol"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    The exposure of bacteria to sub-inhibitory concentrations of antibiotics is of biological significance since it can occur in vivo under many circumstances, including low-dose treatment, poor adherence to a regimen, poor drug penetration, drug-drug interactions, and antibiotic resistance of the pathogen. In this study, we investigated the effects of subinhibitory concentrations of four antibiotics: ampicillin, ceftriaxone, gentamicin, and norfloxacin, which are commonly used in clinical settings and on cell morphology and biofilm formation in\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    as one of the leading causes of nosocomial and biofilm-associated infections. Nine clinical\n                    <jats:italic>S. aureus<\/jats:italic>\n                    biofilm-producing isolates and two known biofilm-producing reference strains,\n                    <jats:italic>S. aureus<\/jats:italic>\n                    ATCC 29213 and\n                    <jats:italic>S. aureus<\/jats:italic>\n                    ATCC 6538, were used in this study. Sub-MICs of beta-lactam antibiotics (ampicillin and ceftriaxone) significantly induced biofilm formation in\n                    <jats:italic>S. aureus<\/jats:italic>\n                    ATCC 29213 and\n                    <jats:italic>S. aureus<\/jats:italic>\n                    ATCC 6538 and in six clinical isolates out of the nine selected isolates when compared with the antibiotic-free control group (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u2009\n                    <jats:italic>0.05<\/jats:italic>\n                    ), with an approximately 2- to 2.5-fold increase. Gentamicin and norfloxacin induced biofilms in\n                    <jats:italic>S. aureus<\/jats:italic>\n                    ATCC 29213 and\n                    <jats:italic>S. aureus<\/jats:italic>\n                    ATCC 6538, while gentamicin and norfloxacin induced biofilms only in three and two of the nine tested isolates, respectively (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u2009\n                    <jats:italic>0.05<\/jats:italic>\n                    ). The chemical nature of the biofilm matrix produced by half the MIC of ceftriaxone in the six isolates that showed increased biofilm was all non-polysaccharide in composition (PIA-independent). Gene expression of biofilm-encoding genes\n                    <jats:italic>atl<\/jats:italic>\n                    and\n                    <jats:italic>sarA<\/jats:italic>\n                    in biofilms of the two tested strains (\n                    <jats:italic>S. aureus<\/jats:italic>\n                    ATCC 6538) and clinical strain (\n                    <jats:italic>S. aureus<\/jats:italic>\n                    16) showed a significant upregulation after exposure to half MIC of ceftriaxone. Additionally, the bacterial cell morphological changes in planktonic cells caused by half MIC of ceftriaxone were evaluated by scanning electron microscopy, which demonstrated a significant cell enlargement when compared with the antibiotic-free control (\n                    <jats:italic>P<\/jats:italic>\n                    \u2009&lt;\u2009\n                    <jats:italic>0.05<\/jats:italic>\n                    ), and some deformed cells were also noticed. In\n                    <jats:italic>S. aureus<\/jats:italic>\n                    clinical isolates, sub-MICs of ampicillin, ceftriaxone, gentamicin, and norfloxacin may stimulate substantial production of biofilm, which could have important clinical significance and make infection treatment challenges. Further, in vivo research is needed to fully comprehend how sub-MIC of antibiotics can affect biofilm formation in clinical settings. Additionally, more research is required to reveal the clinical implications of the morphological alterations in\n                    <jats:italic>S. aureus<\/jats:italic>\n                    brought on by exposure to ceftriaxone at concentrations below its MIC.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Graphical Abstract<\/jats:bold>\n                  <\/jats:p>","DOI":"10.1007\/s42770-023-01177-x","type":"journal-article","created":{"date-parts":[[2023,11,18]],"date-time":"2023-11-18T01:02:50Z","timestamp":1700269370000},"page":"297-308","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Sub-inhibitory concentrations of ceftriaxone induce morphological alterations and PIA-independent biofilm formation in Staphylococcus aureus"],"prefix":"10.1007","volume":"55","author":[{"given":"Ahmed","family":"Azzam","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riham M.","family":"Shawky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2315-6801","authenticated-orcid":false,"given":"Taghrid S.","family":"El-Mahdy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,11,18]]},"reference":[{"key":"1177_CR1","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1007\/978-3-540-75418-3_10","volume":"322","author":"M Otto","year":"2008","unstructured":"Otto M (2008) Staphylococcal biofilms. 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