{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T10:18:45Z","timestamp":1793873925668,"version":"4.6.1"},"reference-count":310,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T00:00:00Z","timestamp":1746489600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Deanship of Scientific Research at Imam Mohammad Ibn Saud Islamic University (IMSIU)","award":["IMSIU-DDRSP2501"],"award-info":[{"award-number":["IMSIU-DDRSP2501"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Staphylococcus aureus is a formidable human pathogen responsible for infections ranging from superficial skin lesions to life-threatening systemic diseases. This review synthesizes current knowledge on its pathogenesis, emphasizing colonization dynamics, virulence mechanisms, biofilm formation, and antibiotic resistance. By analyzing studies from PubMed, Scopus, and Web of Science, we highlight the pathogen\u2019s adaptability, driven by surface adhesins (e.g., ClfB, SasG), secreted toxins (e.g., PVL, TSST-1), and metabolic flexibility in iron acquisition and amino acid utilization. Nasal, skin, and oropharyngeal colonization are reservoirs for invasive infections, with biofilm persistence and horizontal gene transfer exacerbating antimicrobial resistance, particularly in methicillin-resistant S. aureus (MRSA). The review underscores the clinical challenges of multidrug-resistant strains, including vancomycin resistance and decolonization strategies\u2019 failure to target single anatomical sites. Key discussions address host\u2013microbiome interactions, immune evasion tactics, and the limitations of current therapies. Future directions advocate for novel anti-virulence therapies, multi-epitope vaccines, and AI-driven diagnostics to combat evolving resistance. Strengthening global surveillance and interdisciplinary collaboration is critical to mitigating the public health burden of S. aureus.<\/jats:p>","DOI":"10.3390\/antibiotics14050470","type":"journal-article","created":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T09:08:56Z","timestamp":1746522536000},"page":"470","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":212,"title":["Staphylococcus aureus: A Review of the Pathogenesis and Virulence Mechanisms"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-5005-9820","authenticated-orcid":false,"given":"Rahima","family":"Touaitia","sequence":"first","affiliation":[{"name":"Department of Natural and Life Sciences, Faculty of Exact Sciences and Natural and Life Sciences, University of Tebessa, Tebessa 12002, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8092-2141","authenticated-orcid":false,"given":"Assia","family":"Mairi","sequence":"additional","affiliation":[{"name":"Laboratoire d\u2019Ecologie Microbienne, Facult\u00e9 des Sciences de la Nature et de la Vie (FSNV), Universit\u00e9 de Bejaia, Bejaia 06000, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6382-8807","authenticated-orcid":false,"given":"Nasir Adam","family":"Ibrahim","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 13318, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8814-5957","authenticated-orcid":false,"given":"Nosiba S.","family":"Basher","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 13318, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2519-4596","authenticated-orcid":false,"given":"Takfarinas","family":"Idres","sequence":"additional","affiliation":[{"name":"Research Laboratory for Management of Local Animal Resources, Rabie Bouchama National Veterinary School of Algiers, Issad ABBAS Street, BP 161 Oued Semar, Algiers 16059, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7479-2456","authenticated-orcid":false,"given":"Abdelaziz","family":"Touati","sequence":"additional","affiliation":[{"name":"Laboratoire d\u2019Ecologie Microbienne, Facult\u00e9 des Sciences de la Nature et de la Vie (FSNV), Universit\u00e9 de Bejaia, Bejaia 06000, Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Getaneh, A. 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