Evolutionary genomics of Staphylococcus aureus : Insights into the origin of methicillin-resistant strains and the toxic shock syndrome epidemic

Abstract

An emerging theme in medical microbiology is that extensive variation exists in gene content among strains of many pathogenic bacterial species. However, this topic has not been investigated on a genome scale with strains recovered from patients with welldefined clinical conditions. Staphylococcus aureus is a major human pathogen and also causes economically important infections in cows and sheep. A DNA microarray representing >90% of the S. aureus genome was used to characterize genomic diversity, evolutionary relationships, and virulence gene distribution among 36 strains of divergent clonal lineages, including methicillin-resistant strains and organisms causing toxic shock syndrome. Genetic variation in S. aureus is very extensive, with Ϸ22% of the genome comprised of dispensable genetic material. Eighteen large regions of difference were identified, and 10 of these regions have genes that encode putative virulence factors or proteins mediating antibiotic resistance. We find that lateral gene transfer has played a fundamental role in the evolution of S. aureus. The mec gene has been horizontally transferred into distinct S. aureus chromosomal backgrounds at least five times, demonstrating that methicillinresistant strains have evolved multiple independent times, rather than from a single ancestral strain. This finding resolves a longstanding controversy in S. aureus research. The epidemic of toxic shock syndrome that occurred in the 1970s was caused by a change in the host environment, rather than rapid geographic dissemination of a new hypervirulent strain. DNA microarray analysis of large samples of clinically characterized strains provides broad insights into evolution, pathogenesis, and disease emergence.DNA microarray ͉ evolution

Molecular tracing of the emergence, adaptation, and transmission of hospital-associated methicillin-resistant Staphylococcus aureus

“…Previous studies have demonstrated that the majority of cases of menstrual TSS are caused by a single clone that corresponds to CC30 (33,34). However, the distribution of the tst gene encoding the toxic shock syndrome toxin 1 (TSST-1) among CC30 subclades has not been previously examined.…”

Identification of resistance and virulence factors in an epidemic Enterobacter hormaechei outbreak strain

“…Comparative genomic hybridization (CGH) is a powerful genetic tool for the study of bacteria (Dobrindt et al, 2003;Fitzgerald et al, 2001Fitzgerald et al, , 2003Fukiya et al, 2004;Israel et al, 2001;Leavis et al, 2007;Lindsay et al, 2006;Paauw et al, 2008;Porwollik et al, 2002;Salama et al, 2000). Most CGH arrays have been designed from annotated wholegenome sequences.…”

DNA Macroarray for Identification and Typing of Staphylococcus aureus Isolates

“…The whole genome sequencing of seven S. aureus strains (N315 [19], Mu50 [19] (11) demonstrated that 2,198 (78%) of the 2,817 COL chromosomal open reading frames (ORFs) represented on a DNA microarray were shared by the 36 analyzed S. aureus isolates from various sources, which belonged to 14 multilocus enzyme electrophoretic types. Ten of the 18 large regions of difference carry genes that encode putative virulence factors and proteins that mediate antibiotic resistance.…”