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This study tested how oxidative stress (H\u2082O\u2082), pH (5\u20139), NaCl (0\u201310%), and human serum (5\u201350%) affect the Newman strain biofilm and key genes (\n                      <jats:italic>icaA<\/jats:italic>\n                      ,\n                      <jats:italic>icaD<\/jats:italic>\n                      ,\n                      <jats:italic>sarA<\/jats:italic>\n                      ). Biofilm was quantified by crystal violet assays and Lowry protein assay methods, and gene expression was measured by quantitative real-time PCR. Biofilm biomass was quantified using crystal violet staining and Lowry protein assays under various environmental conditions. Statistical significance was determined using ANOVA with post hoc analysis (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Hydrogen peroxide induced a dose-dependent reduction in biomass, with significant repression of\n                      <jats:italic>icaA<\/jats:italic>\n                      ,\n                      <jats:italic>icaD<\/jats:italic>\n                      , and\n                      <jats:italic>sarA<\/jats:italic>\n                      expression at 3% H\u2082O\u2082 (\u2264\u200922.8%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Similarly, deviations from neutral pH markedly impaired biofilm formation, with acidic (pH 5) and alkaline (pH 9) conditions reducing biomass by 34.6% and 41.7%, respectively, accompanied by strong downregulation of biofilm-associated genes (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). In contrast, NaCl exerted a biphasic effect: mild osmotic stress (1.25% and 5%) enhanced biofilm biomass (up to 154.2%) in the case of crystal violet assays and at 5% biomass increased to 130.8\u2009\u00b1\u200910.8*%; at 10%, it was 103.5\u2009\u00b1\u20096.1% (no significant change) in the case of protein quantification, and gene expression (\n                      <jats:italic>icaA<\/jats:italic>\n                      160.55%,\n                      <jats:italic>icaD<\/jats:italic>\n                      168.18%,\n                      <jats:italic>sarA<\/jats:italic>\n                      149.8%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001), whereas higher concentrations (\u2265\u200910%) restored expression to near-control levels. Serum exposure produced a threshold-dependent response, with low concentrations (5\u201310%) slightly enhancing gene expression (~\u2009110%), while higher concentrations (20\u201350%) significantly repressed both biomass and transcription, with profound inhibition found at 50% (\n                      <jats:italic>icaA<\/jats:italic>\n                      12.94%,\n                      <jats:italic>icaD<\/jats:italic>\n                      10.88%,\n                      <jats:italic>sarA<\/jats:italic>\n                      12.79%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001). In addition, confocal laser scanning microscopy technique is used as a confirmatory step for qualitative determination of the effects of both various saline and serum concentrations on the biofilm formation, which induces similar results. Environmental stressors modulate\n                      <jats:italic>S. aureus<\/jats:italic>\n                      biofilm formation in a dose-dependent manner via regulation of the\n                      <jats:italic>ica<\/jats:italic>\n                      operon and\n                      <jats:italic>sarA<\/jats:italic>\n                      , offering molecular insights that may guide strategies for biofilm control.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key points<\/jats:title>\n                    <jats:p>\n                      \u2022\n                      <jats:italic>Oxidative stress (H\u2082O\u2082) dose-dependently inhibits S. aureus Newman biofilms.<\/jats:italic>\n                    <\/jats:p>\n                    <jats:p>\n                      \u2022\n                      <jats:italic>Mild NaCl levels enhance biofilm formation via upregulation of ica and sarA.<\/jats:italic>\n                    <\/jats:p>\n                    <jats:p>\n                      \u2022\n                      <jats:italic>High serum concentrations (\u2265\u200920%) suppress biofilm biomass and gene expression.<\/jats:italic>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1007\/s00253-026-13781-6","type":"journal-article","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T17:34:57Z","timestamp":1774373697000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Environmental and chemical modulation of Staphylococcus aureus Newman biofilm formation"],"prefix":"10.1007","volume":"110","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5193-9662","authenticated-orcid":false,"given":"Ahmed R.","family":"Ragab","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2745-3811","authenticated-orcid":false,"given":"Ahmed R.","family":"El\u2010Sheakh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1147-336X","authenticated-orcid":false,"given":"Shokri M.","family":"Shafik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,24]]},"reference":[{"key":"13781_CR1","doi-asserted-by":"publisher","first-page":"388","DOI":"10.1016\/j.micpath.2010.07.005","volume":"49","author":"NM Abraham","year":"2010","unstructured":"Abraham NM, Jefferson KK (2010) A low molecular weight component of serum inhibits biofilm formation in Staphylococcus aureus. 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