Complete genomes of two clinical Staphylococcus aureus strains: Evidence for the rapid evolution of virulence and drug resistance

Abstract

Staphylococcus aureus is an important nosocomial and communityacquired pathogen. Its genetic plasticity has facilitated the evolution of many virulent and drug-resistant strains, presenting a major and constantly changing clinical challenge. We sequenced the Ϸ2.8-Mbp genomes of two disease-causing S. aureus strains isolated from distinct clinical settings: a recent hospital-acquired representative of the epidemic methicillin-resistant S. aureus EMRSA-16 clone (MRSA252), a clinically important and globally prevalent lineage; and a representative of an invasive communityacquired methicillin-susceptible S. aureus clone (MSSA476). A comparative-genomics approach was used to explore the mechanisms of evolution of clinically important S. aureus genomes and to identify regions affecting virulence and drug resistance. The genome sequences of MRSA252 and MSSA476 have a well conserved core region but differ markedly in their accessory genetic elements. MRSA252 is the most genetically diverse S. aureus strain sequenced to date: Ϸ6% of the genome is novel compared with other published genomes, and it contains several unique genetic elements. MSSA476 is methicillin-susceptible, but it contains a novel Staphylococcal chromosomal cassette (SCC) mec-like element (designated SCC 476), which is integrated at the same site on the chromosome as SCCmec elements in MRSA strains but encodes a putative fusidic acid resistance protein. The crucial role that accessory elements play in the rapid evolution of S. aureus is clearly illustrated by comparing the MSSA476 genome with that of an extremely closely related MRSA community-acquired strain; the differential distribution of large mobile elements carrying virulence and drug-resistance determinants may be responsible for the clinically important phenotypic differences in these strains.

Broad host range plasmids can invade an unexpectedly diverse fraction of a soil bacterial community

“…These groups include the proteobacterial Enterobacteria, Pseudomonas or Campylobacter, and also groups from other phyla such as Fusobacterium, Streptococcus and Staphylococcus, most of which are treated with antibiotic therapy. Especially the acquisition of new antibiotic resistance genes through plasmid-mediated gene transfer may push the pathogenic potential of Staphylococcus, originating from rapid evolution of virulence and drug resistance (Holden et al, 2004), even further.…”

Analysis of prophages harbored by the human-adapted subpopulation of Staphylococcus aureus CC398

“…Microarrays were produced by in situ synthesis of a set of 15,600 60-mer long oligonucleotide probes (Agilent, Palo Alto, CA, USA). The probe set included 8877 probes covering approximately 95% of all ORFs annotated in strains N315 and Mu50 (Kuroda et al, 2001), MW2 (Baba et al, 2002), COL (Gill et al, 2005), NCTC 8325 (Gillaspy et al, 2006), USA300 (Diep et al, 2006), MRSA252 and MSSA476 (Holden et al, 2004) and including those on their plasmids. Each gene was covered by one to 12 probes depending on gene length.…”

Genome dynamics in a natural archaeal population

“…However, in most cases only a single representative of a particular lineage has been analyzed genomically. Where multiple strain genomes are available, the organisms are typically pathogens, and the strains are derived from distinct localities (1)(2)(3)(4)(5). Lacking are comparative population genomic studies that include analysis of an isolate versus an environmental population of the same species obtained from the same site.…”