It was immediately recognized that methicillin resistance was mechanistically different than

penicillin resistance in that the MRSA phenotype did not involve direct inactivation of the drug. Rather, resistance was mediated through the acquisition of an alternative penicillin-binding protein (PBP2a) with lowered affinity for β-lactam antibiotics. Within 20 years after the first discovery of MRSA, it became a leading cause of hospital-acquired infections (Archer & Mayhall, 1983). Currently, it can still be responsible for nearly 60% of skin/soft tissue infections Selleckchem AZD5363 presenting to US emergency rooms (Moran et al., 2006). The methicillin resistance determining PBP2a is encoded by mecA harbored on a mobile genetic element (MGE), staphylococcal cassette chromsome (SCCmec). A nearly identical homologue, now thought to be the ancestral mecA, was recently discovered in Staphylococcus fleuretti, an animal colonizing staphylococcal species (Tsubakishita et al., 2010). Unlike a previously identified mecA homologue in Staphylococcus sciuri that does not confer Talazoparib chemical structure methicillin resistance

(Couto et al., 1996), S. fleuretti is fully resistant to β-lactam antibiotics. Interestingly, the S. fleuretti mecA homologue is not found on a mobile SCC, but rather in the core chromosome between the mevalonate biosynthetic and xylose utilization operons, explaining the presence of mva and xyl gene fragments in some S. aureus SCCmec elements (Tsubakishita

et al., 2010). These mobile islands have diversified considerably over the 50-year history of MRSA such that there are currently eight distinct SCCmec types circulating among S. aureus as well as some species of coagulase negative staphylococci (Center for Disease Control & Prevention, 2009a). SCCmec elements can vary greatly in size and composition with the largest (SCCmec type II) spanning 52 kb and additionally encoding erythromycin, spectinomycin and tobramycin resistance determinants (Katayama et al., 2000). Depending Sitaxentan on the particular SCCmec type, these mobile islands peppered with insertion sequence (IS) elements, transposons and integrated plasmids, can confer multidrug resistance determinants that significantly diminish treatment options in a clinical setting. Thus, in addition to methicillin resistance, MRSA isolates have evolved multidrug resistance leading to what the popular press refers to as an emerging superbug (McKenna, 2010). After 1961, MRSA spread worldwide causing significant morbidity and mortality almost entirely as hospital-acquired infections. Advances in molecular epidemiology allowed for in-depth analyses of MRSA spread and expansion at the evolutionary level. For instance, spa-typing (polymorphisms in Protein A coding sequence) and SCCmec-typing discriminated unrelated clones and identified clusters of related MRSA lineages responsible for disease (Shopsin et al., 1999; Okuma et al., 2002).