Evolution and pathogenesis of Staphylococcus aureus
Staphylococcus aureus is an extraordinarily versatile pathogen that can survive in hostile environmental conditions, colonize mucous membranes and skin, and can cause severe, nonpurulent, toxin-mediated disease or invasive pyogenic infections in humans. In the 1940s, penicillin G was the treatment of choice for infections caused by S. aureus. However, since the 1960s, S. aureus strains resistant to the penicillinase-resistant penicillins, as represented by the original member of the class, methicillin, have gradually emerged worldwide. These strains have been historically referred to as methicillin-resistant S. aureus (MRSA) and are resistant to all beta-lactam antibiotics. Recently, these strains have become multidrug-resistant.
Comparative genomics, including comparison at the sequence, transcriptome, and proteome levels, has been an increasingly important approach for scientists to improve knowledge on the pathogenesis and drug resistance of S. aureus. For example, vancomycin, as the last resort against multi-resistant MRSA, has gradually lost its potency due to the appearance of vancomycin-resistant strains. Whereas high-level vancomycin resistance in S. aureus has been shown to rely on horizontal transfer of vanA from Enterococcus faecalis, the mechanisms underlying vancomycin-intermediate-resistant remain poorly understood.
Multilocus sequence typing reveals a highly clonal structure for S. aureus. Although infrequently occurring across clonal complexes, homologous recombination still contributed to the evolution of this species over the long term. Genome sequencing of nine S. aureus strains has helped identify a number of virulence factors, but the key determinants for infection are still unknown. Comparison of commensal and pathogenic strains shows no difference in diversity or clonal assignments. Thus, phage dynamics and global transcriptome shifts are considered to be responsible for the pathogenicity. Community-acquired methicillin-resistant S. aureus (C-MRSA) is characterized by a short SCCmec and the presence of a Panton-Valentine leukocidin locus, but no studies have proven their exact biologic roles in C-MRSA infection, indicating the existence of other mechanisms for the genesis of C-MRSA.
- MRSA: Methicillin-resistant Staphylococcus aureus
- Beating antibiotic resistance
- Bacterial toxins
- Novel treatments for MRSA