Reemergence of antibiotic-resistant Staphylococcus aureus in the genomics era

Abstract

Staphylococcus aureus is the leading cause of bacterial infections in developed countries and produces a wide spectrum of diseases, ranging from minor skin infections to fatal necrotizing pneumonia.Although S. aureus infections were historically treatable with common antibiotics, emergence of drug-resistant organisms is now a major concern.Methicillin-resistant S. aureus (MRSA) was endemic in hospitals by the late 1960s, but it appeared rapidly and unexpectedly in communities in the 1990s and is now prevalent worldwide.This Review focuses on progress made toward understanding the success of community-associated MRSA as a human pathogen, with an emphasis on genomewide approaches and virulence determinants.Recent emergence of CA-MRSA The molecular epidemiology and evolution of MRSA is a topic too expansive for this Review, but several key features of CA-MRSA strains merit mention.Based on molecular typing and microarray approaches, S. aureus can be grouped broadly into at least 10 major lineages, named clonal complexes (Table 1) (20-22).Pulsed-field gel electrophoresis is commonly used to identify S. aureus isolates in the United States, and for simplicity, here we use this typing system to describe S. aureus strains (Sidebar 1) (23).In 2003, pulsedfield gel electrophoresis types USA100, USA200, USA500, USA600, and USA800 were the predominant health care-associated strains, whereas USA300 and USA400 were the most abundant CA-MRSA strains (23).MRSA strains can be characterized further by at least five distinct staphylococcal cassette chromosome mec (SCCmec) types (I-V), mobile genetic elements that encode methicillin resistance.Health care-associated MRSA strains historically contain predominantly SCCmecI-III, whereas CA-MRSA typically carries SCCmecIV (24,25).SCCmecIV, which is smaller than SCCmecI-III, lacks other antibiotic resistance elements and appears to impart little or no fitness cost to the organism (24).Consistent with this idea, CA-MRSA strains in general have faster growth rates than health care-associated MRSA strains (24).In addition to SCC-mecIV, CA-MRSA strains carry genes encoding a toxin known as Panton-Valentine leukocidin (PVL, discussed below), and both are often used as markers for CA-MRSA. CA-MRSA in the clinicClinical epidemiology and disease.CA-MRSA infections appear to have emerged first among indigenous people of the remote Kimberley region of Western Australia in the early 1990s (18, 26).The first Conflict of interest:The authors have declared that no conflict of interest exists.