Staphylococcus aureus: A pathogen with still unresolved issues

Staphylococcus aureus is a major human pathogen, and considerable research efforts have been put forward to improve our understanding of its complex pathogenesis. In spite of these efforts, the burden of staphylococcal infections is still on the rise. This review focuses on a selected set of crucial unresolved questions regarding this pathogen, namely: (i) the nature of the driving forces behind the rise and decline of methicillin-resistant S. aureus (MRSA) clones; (ii) the mechanisms by which a commensal becomes a pathogen; (iii) the molecular underpinnings of toxin overexpression in hypervirulent MRSA clones such as USA300; and (iv) the repeated failures of anti-S. aureus vaccine approaches.