Staphylococcus aureus Pathogenesis, Resistance, and Microbiome Interactions Original paper

What was reviewed?

This comprehensive review examined the pathogenesis and virulence mechanisms of Staphylococcus aureus (S. aureus), with a particular focus on its colonization dynamics, immune evasion strategies, antibiotic resistance mechanisms, and emerging therapeutic interventions. The paper synthesizes findings from over 300 references spanning microbial physiology, molecular biology, epidemiology, and therapeutic research. The review highlights the adaptability of S. aureus as both a commensal and an opportunistic pathogen and outlines its ability to persist in diverse anatomical niches (e.g., nares, throat, gut, urogenital tract), evade immune responses, and establish both acute and chronic infections through biofilm formation and toxin production.

Who was reviewed?

The review references a broad spectrum of literature, including in vitro experiments, in vivo murine models, clinical epidemiological studies, and molecular genetic analyses of both methicillin-resistant (MRSA) and methicillin-susceptible (MSSA) S. aureus strains. It includes data on specific populations such as surgical patients, immunocompromised individuals, healthcare workers, and the general community, highlighting geographic differences in colonization and resistance patterns across continents.

Most important findings

Staphylococcus aureus exhibits a remarkable capacity for anatomical colonization, microbial manipulation, immune evasion, and antibiotic resistance, which collectively underpin its pathogenic success. The organism utilizes specialized adhesins to establish persistent colonization in the nasal vestibule, oropharynx, skin, gastrointestinal, and urogenital tracts, often in the form of biofilms. Within the microbiome, S. aureus plays a central role in shaping community dynamics via siderophore-mediated iron sharing, particularly through staphyloferrin A and B, which support the growth of neighboring taxa such as Corynebacterium and Staphylococcus lugdunensis. Cytotoxins such as Panton-Valentine leukocidin (PVL), α-hemolysin, and superantigens enable immune suppression and tissue necrosis, with PVL linked to severe SSTIs and necrotizing pneumonia. Antibiotic resistance is multifactorial and involves mecA/mecC (methicillin), vanA/vanB (vancomycin), and aminoglycoside-modifying enzymes (AMEs), with horizontal gene transfer via SCCmec elements and phages accelerating dissemination. Biofilm-related genes and regulatory systems such as agr and sarA further fine-tune virulence expression, promoting persistence and complicating eradication. These findings underscore the importance of considering both the pathogen’s molecular arsenal and its interaction with the host microbiota in designing effective clinical interventions.

Summary Table of Key Pathogenic Features of S. aureus

Key implications

This review emphasizes that Staphylococcus aureus is not a solitary pathogen but one deeply intertwined with host microbiota and environmental cues. Its adaptability through mobile genetic elements, virulence plasticity, and metabolic versatility positions it as both a microbiome disruptor and a persistent pathogen. The failure of current decolonization strategies, particularly in the throat and perineum, underscores the necessity for niche-specific interventions and new vaccine targets that account for immune evasion. Moreover, the review encourages the adoption of phage therapy, CRISPR antimicrobials, and multi-target vaccines to overcome the challenges posed by MRSA and PVL-positive strains. For microbiome-focused clinicians, understanding S. aureus colonization dynamics and its interplay with siderophore-mediated microbial support systems is essential for holistic therapeutic strategies.