How Clonal Is Staphylococcus aureus ?

Abstract

Staphylococcus aureus is an important human pathogen and represents a growing public health burden owing to the emergence and spread of antibiotic-resistant clones, particularly within the hospital environment. Despite this, basic questions about the evolution and population biology of the species, particularly with regard to the extent and impact of homologous recombination, remain unanswered. We address these issues through an analysis of sequence data obtained from the characterization by multilocus sequence typing (MLST) of 334 isolates of S. aureus, recovered from a well-defined population, over a limited time span. We find no significant differences in the distribution of multilocus genotypes between strains isolated from carriers and those from patients with invasive disease; there is, therefore, no evidence from MLST data, which index variation within the stable "core" genome, for the existence of hypervirulent clones of this pathogen. Examination of the sequence changes at MLST loci during clonal diversification shows that point mutations give rise to new alleles at least 15-fold more frequently than does recombination. This contrasts with the naturally transformable species Neisseria meningitidis and Streptococcus pneumoniae, in which alleles change between 5-and 10-fold more frequently by recombination than by mutation. However, phylogenetic analysis suggests that homologous recombination does contribute toward the evolution of this species over the long term. Finally, we note a striking excess of nonsynonymous substitutions in comparisons between isolates belonging to the same clonal complex compared to isolates belonging to different clonal complexes, suggesting that the removal of deleterious mutations by purifying selection may be relatively slow.Staphylococcus aureus is a gram-positive pathogen responsible for a wide range of human disease, including septicemia; endocarditis and pneumonia; and wound, bone, and joint infections. Although the vast majority of infections by S. aureus result in asymptomatic carriage, this species nevertheless represents a serious public health burden, particularly in the hospital setting, where clones resistant to methicillin and other classes of antibiotics are endemic and insensitivity to vancomycin is on the increase. Although S. aureus is considered to be an opportunistic pathogen, it is possible that certain clones are more prone to cause invasive disease than are others, due to the presence of virulence factors that increase their chance of gaining access to normally sterile sites. Although many putative virulence factors have been identified in the S. aureus genome (17), the differences in pathogenic potential between naturally occurring isolates remain largely unaddressed.The extent to which homologous recombination contributes to the emergence and subsequent diversification of clones is also at present unclear, although this question has important implications both for the choice of the most appropriate typing strategy for effective epidemiological surveilla...

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