Browsing by Author "Gill, Steven R"

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    Potential associations between severity of infection and the presence of virulence-associated genes in clinical strains of Staphylococcus aureus.
    (PLoS One, 2011-04-26) Gill, Steven R; McIntyre, Lauren M; Nelson, Charlotte L; Remortel, Brian; Rude, Tom; Reller, L Barth; Fowler, Vance G
    BACKGROUND: The clinical spectrum of Staphylococcus aureus infection ranges from asymptomatic nasal carriage to osteomyelitis, infective endocarditis (IE) and death. In this study, we evaluate potential association between the presence of specific genes in a collection of prospectively characterized S. aureus clinical isolates and clinical outcome. METHODOLOGY/PRINCIPAL FINDINGS: Two hundred thirty-nine S. aureus isolates (121 methicillin-resistant S. aureus [MRSA] and 118 methicillin-susceptible S. aureus [MSSA]) were screened by array comparative genomic hybridization (aCGH) to identify genes implicated in complicated infections. After adjustment for multiple tests, 226 genes were significantly associated with severity of infection. Of these 226 genes, 185 were not in the SCCmec element. Within the 185 non-SCCmec genes, 171 were less common and 14 more common in the complicated infection group. Among the 41 genes in the SCCmec element, 37 were more common and 4 were less common in the complicated group. A total of 51 of the 2014 sequences evaluated, 14 non-SCCmec and 37 SCCmec, were identified as genes of interest. CONCLUSIONS/SIGNIFICANCE: Of the 171 genes less common in complicated infections, 152 are of unknown function and may contribute to attenuation of virulence. The 14 non-SCCmec genes more common in complicated infections include bacteriophage-encoded genes such as regulatory factors and autolysins with potential roles in tissue adhesion or biofilm formation.
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    Potential Influence of Staphylococcus aureus Clonal Complex 30 Genotype and Transcriptome on Hematogenous Infections.
    (Open Forum Infect Dis, 2015-09) Sharma-Kuinkel, Batu K; Mongodin, Emmanuel F; Myers, Jason R; Vore, Kelly L; Canfield, Greg S; Fraser, Claire M; Rude, Thomas H; Fowler, Vance G; Gill, Steven R
    Background.  The contemporary Staphylococcus aureus clonal complex (CC) 30 lineage is associated with complicated infections, including endocarditis and osteomyelitis. This lineage diverged from the phage-type 80/81 S aureus clone responsible for a major bacterial epidemic of the 20th century. The genome and transcriptome features that contribute to complicated infections of the CC30 lineage are unknown. Methods.  Twenty-nine clinical methicillin-resistant S aureus (MRSA) strains (8 from CC30 and 21 from other major CCs were evaluated for virulence using murine and Galleria mellonella sepsis models. Genomic features of CC30 were identified by comparative genome sequencing and RNA-Seq transcriptome analysis of the 29 strains and 31 previously sequenced S aureus genomes. Results.  The CC30 isolates displayed lower virulence in the sepsis models compared with other CCs [P < .0001]. Comparisons of orthologous proteins and transcriptome analysis identified genes (eg, nitric oxide reductase) and changes in metabolic pathways (eg, pyrimidine metabolism) that contribute to the distinct CC30 phenotype. Previously reported nonsynonymous single-nucleotide polymorphisms (SNPs) were found in accessory gene regulator C (agrC) and α-hemolysin (hla), molecules important for virulence. Additional nonsynonymous SNPs conserved across clinical CC30 isolates when compared with the first sequenced contemporary CC30 clone, MRSA-16, were identified in multiple genes, suggesting continuing evolutionary divergence in this lineage. Conclusions.  Genomic and transcriptional analyses suggest that the CC30 lineage has acquired metabolic features that contribute to persistent and complicated infections. Absence of sepsis-induced mortality in animal models may be due in part to its unique genomic profile and suggests that specific genotypes of S aureus elicit distinct types of infection types.