Genome Diversification in
            <i>Staphylococcus aureus</i>
            : Molecular Evolution of a Highly Variable Chromosomal Region Encoding the Staphylococcal Exotoxin-Like Family of Proteins

Fitzgerald, J. Ross; Reid, Sean D.; Ruotsalainen, Eeva; Tripp, Timothy J.; Liu, Meng Yao; Cole, Robert L.; Kuusela, Pentti; Schlievert, Patrick M.; Järvinen, Asko; Musser, James M.

doi:10.1128/iai.71.5.2827-2838.2003

Cited by 115 publications

(105 citation statements)

References 19 publications

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“…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.…”

Section: Introductionmentioning

confidence: 99%

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

Paauw

Caspers²,

Hall

et al. 2009

Microbiology

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Bacterial strains differ in their ability to cause hospital outbreaks. Using comparative genomic hybridization, Enterobacter cloacae complex isolates were studied to identify genetic markers specific for Enterobacter cloacae complex outbreak strains. No outbreak-specific genes were found that were common in all investigated outbreak strains. Therefore, the aim of our study was to identify specific genetic markers for an Enterobacter hormaechei outbreak strain (EHOS) that caused a nationwide outbreak in The Netherlands. Most EHOS isolates carried a large conjugative plasmid (pQC) containing genes encoding heavy-metal resistance, mobile elements, pili-associated proteins and exported proteins as well as multiple-resistance genes. Furthermore, the chromosomally encoded high-pathogenicity island (HPI) was highly associated with the EHOS strain. In addition, other DNA fragments were identified that were associated with virulence: three DNA fragments known to be located on a virulence plasmid (pLVPK), as well as phage-and plasmid-related sequences. Also, four DNA fragments encoding putative pili with the most homology to pili of Salmonella enterica were associated with the EHOS. Finally, four DNA fragments encoding putative outer-membrane proteins were negatively associated with the EHOS. In conclusion, resistance and putative virulence genes were identified in the EHOS that may have contributed to increased epidemicity. The high number of genes detected in the EHOS that were related to transferable elements reflects the genomic plasticity of the E. cloacae complex and may explain the emergence of the EHOS in the hospital environment. INTRODUCTIONIn the pre-antibiotic era, isolates of the Enterobacter cloacae complex were not detected in surveys of nosocomial bacteria; they were first described as nosocomial pathogens in the 1970s (Sanders & Sanders, 1997). In 2001, Enterobacter spp. caused 7 % of nosocomial infections in intensive care units in the USA (Jones, 2003;Streit et al., 2004). Therefore, the E. cloacae complex can be considered as an emerging pathogen, of which Enterobacter hormaechei is the most commonly isolated nosocomial pathogen (Delmas et al., 2006;Paauw et al., 2008). A nationwide outbreak occurred with an E. hormaechei outbreak strain (EHOS) in The Netherlands . This strain disseminated throughout hospitals despite adequate implementation of internationally accepted infection-prevention guidelines and caused invasive infections in more than 100 patients (Paauw et al., 2007). Previous studies showed that most EHOS isolates carried the conjugative plasmid pQC, with several complex integrons containing aadB, bla CTX-M-9 and qnrA1 genes that encoded resistance to aminoglycosides and thirdgeneration cephalosporins, and reduced susceptibility to fluoroquinolones, respectively . However, it was also shown that other Enterobacteriaceae including other E. cloacae complex isolates with the pQC did not become highly epidemic like the EHOS (Paauw et al., 2007). Furthermore, of aminoglycoside-susceptible E. cloa...

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Section: Introductionmentioning

confidence: 99%

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

Paauw

Caspers²,

Hall

et al. 2009

Microbiology

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“…||Not all of the genes encoded by the ssl locus were investigated; only the seven genes that lie in the variable region of the ssl locus were tested for. It has been demonstrated that strain COL expresses its ssl genes concurrently and that multiple ssl genes are expressed during human infection, as evidenced by Western immunoblotting using sera from acute and convalescent patients (Arcus et al, 2002;Fitzgerald et al, 2003;Al-Shangiti et al, 2005). However, not all of the Ssl proteins are immunogenic.…”

Section: Discussionmentioning

confidence: 99%

“…The ssl locus had been reported in 49 S. aureus isolates from humans, 8 isolates from cows, 2 isolates from sheep, 2 isolates from poultry and 2 isolates of unknown species origin (Fitzgerald et al, 2003). However, no group had looked for the individual ssl genes with the exception of the set1 allelic variant of the archetypal gene ssl7 (Williams et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

“…At the start of this work very limited data were available on the occurrence of individual ssl genes in S. aureus isolates from animals (Fitzgerald et al, 2003). The aims of this study were to develop a PCR-based screening method for ssl genes within the variable region of the vSaa genomic island and to investigate the occurrence of these genes in isolates of S. aureus of animal origin.…”

Section: Introductionmentioning

confidence: 99%

“…The vSaa island is flanked upstream by a putative transposase gene, and downstream by an incomplete restriction and modification system (the hsdS and hsdM genes) forming part of a three-component restriction/modification system (HsdS, HsdM and HsdR) that is believed to maintain the locus in the genome (Kuroda et al, 2001). Although the crystal structures of the Ssl5 and Ssl7 proteins revealed that these had overall folding characteristics and the classical two-domain structure of the SAg family, the major histocompatibility complex-binding site of superantigens had been lost, accounting for the inability of Ssl proteins to induce T-cell proliferation (Arcus et al, 2002;Al-Shangiti et al, 2004) Microarray analysis using 63 isolates from humans, sheep, cows and poultry (Fitzgerald et al, 2003) showed that the ssl locus was present in all of the S. aureus isolates tested, but varied in size from 12 to 17 kb and displayed high levels of sequence variation. It was theorized that horizontal gene transfer, recombination events, and loss of ssl genes had led to this diversity.…”

Section: Introductionmentioning

confidence: 99%

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Occurrence of ssl genes in isolates of Staphylococcus aureus from animal infection

Smyth

Meaney

Hartigan

et al. 2007

Journal of Medical Microbiology

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The occurrence of 7 of the 11 known ssl genes that are found within the vSaa genomic island of Staphylococcus aureus and encode the novel Ssl family of exoproteins was examined in isolates from cows (42 isolates), goats (4 isolates), sheep (1 isolate), rabbits (3 isolates) and chickens (2 isolates). Based on seven S. aureus genome sequences for human strains NCTC 8325, N315, Mu50, COL, MRSA 252, MW2 and MSSA-476, and bovine strain RF122, along with the ssl reference gene sequences from strains NCTC 6571, FRI326 and NCTC 8325, ClustalWgenerated alignments were used to design PCR primers for unique regions of the ssl genes that are present in the allelic variants of each, except for the ssl4 gene for which specific primers for the set2 and set9 allelic variants were designed individually. The genotypes of isolates were determined using random amplified polymorphic DNA (RAPD) typing. All of the animal-associated S. aureus isolates contained an ssl locus, but there were minor variations in the number of ssl genes present. Forty-nine of the animal isolates possessed a vSaa genomic island containing the ssl3 (set8), ssl5 (set3/set10), ssl7 (set1/set11), ssl8 (set12), ssl9 (set5/set13) and ssl10 (set4/set14) genes. One bovine and one goat isolate lacked the ssl3 gene. The ssl9 gene was absent in one bovine isolate. The goat isolate lacking the ssl3 gene was the only animal isolate that possessed the set2 allele of the ssl4 gene. PCR for the set9 allele of the ssl4 gene was inconclusive. Isolates that showed identical RAPD fingerprints had the same complement of ssl genes, but the ssl gene pattern was not RAPD-type specific. Southern blot hybridization showed similar ssl gene RFLPs in isolates of the same RAPD type.

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Pathogenic Staphylococci: Lessons from Comparative Genomics

Ohlsen¹,

Eckart²,

Hüttinger³

et al. 2006

Pathogenomics

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Genome Diversification in Staphylococcus aureus : Molecular Evolution of a Highly Variable Chromosomal Region Encoding the Staphylococcal Exotoxin-Like Family of Proteins

Cited by 115 publications

References 19 publications

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

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

Occurrence of ssl genes in isolates of Staphylococcus aureus from animal infection

Pathogenic Staphylococci: Lessons from Comparative Genomics

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