From colonisation to immune evasion: a synthesis of the interaction strategies that drive Staphylococcus aureus infection

Staphylococcus aureus (S. aureus) remains a major human and veterinary pathogen, driven by multiple virulence processes, including toxin activity, biofilm formation, metabolic adaptation, regulatory networks, antimicrobial resistance, strain-specific traits. Many of these processes involve host-pathogen protein-protein interactions (PPIs). This review focuses on PPIs as a major mechanistic layer that links adhesion, invasion and immune evasion across infection stages. We synthesise available evidence to explain how selected PPIs support the transition from carriage to invasive disease. We first compare surface adhesins that use distinct binding architectures, including Dock, Lock and Latch, the Collagen Hug and the tandem β-zipper, to achieve force-resilient attachment under physiological shear. We then organise immune-evasion PPIs along the chronology of host defence, from early sensing and antimicrobial barriers to phagocyte recruitment, complement and opsonisation, intraphagosomal killing and adaptive immunity. This staged view highlights how mechanoadaptive anchoring, redundancy and multifunctionality can contribute to robust infection phenotypes and suggests therapeutic opportunities involving allosteric modulation, decoy-based restoration of host pathways and multi-target biologics.