Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Genome-scale analysis of Staphylococcus aureus reveals host-specific diversification of the core genome.

ABSTRACT: Staphylococcus aureus causes disease in humans and a wide array of animals. Of note, S. aureus mastitis of ruminants, including cows, sheep and goats, results in major economic losses worldwide. Extensive variation in genome content exists among S. aureus pathogenic clones. However, the genomic variation among S. aureus strains infecting different animal species has not been well examined. To investigate variation in the genome content of human and ruminant S. aureus we carried out whole genome PCR scanning (WGPS), comparative genomic hybridizations (CGH), and directed DNA sequence analysis of strains of human, bovine, ovine, and caprine origin. Extensive variation in genome content was discovered including host- and ruminant-specific genetic loci. Ovine and caprine strains were genetically allied whereas bovine strains were heterogenous in gene content. As expected, mobile genetic elements such as pathogenicity islands and bacteriophages contributed to the variation in genome content between strains. However, remarkably, most host-specific differences were restricted to regions of the conserved core genome, which contained allelic variation in genes encoding proteins of known and unknown function. Many of these proteins are predicted to be exported and could play a role in host-pathogen interactions. These data suggest that diversification of the core genome may be more important than acquisition of novel genes for S. aureus host-adaptation. The host-specific determinants identified by the whole-genome approaches adopted in the current study represent excellent targets for studies of the evolution and molecular basis of S. aureus host specificity. Keywords: Strain vs strain eleven strains of Sa were compared at the DNA level in triplicate.

ORGANISM(S): Staphylococcus aureus

SUBMITTER: Dan Sturdevant

PROVIDER: E-GEOD-10187 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Genome-wide analysis of ruminant Staphylococcus aureus reveals diversification of the core genome.

Ben Zakour Nouri L NL Sturdevant Daniel E DE Even Sergine S Guinane Caitriona M CM Barbey Corinne C Alves Priscila D PD Cochet Marie-Françoise MF Gautier Michel M Otto Michael M Fitzgerald J Ross JR Le Loir Yves Y

Journal of bacteriology 20080620 19

Staphylococcus aureus causes disease in humans and a wide array of animals. Of note, S. aureus mastitis of ruminants, including cows, sheep, and goats, results in major economic losses worldwide. Extensive variation in genome content exists among S. aureus pathogenic clones. However, the genomic variation among S. aureus strains infecting different animal species has not been well examined. To investigate variation in the genome content of human and ruminant S. aureus, we carried out whole-genom ...[more]

PMID: 18567666

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Project description:Background: Staphylococcus aureus is a major pathogen of humans and animals and rapidly emerging antibiotic-resistant strains have further increased the severity of this health issue. Host genetics influence susceptibility to S. aureus infections, and genes determining infection outcome should be identified to analyze immune-based therapies as an alternative to antibiotics. Here, we used outbred animals from a divergent selection on susceptibility towards Staphylococcus infection to explore host immunogenetics. Methodology/Principal Findings: We investigated how dendritic cells respond to heat-inactivated S. aureus and whether dendritic cells from animals with different degree of susceptibility have distinct gene expression profiles. We measured expression levels of 15K probes from in vitro S. aureus-stimulated bone marrow-derived dendritic cells at three different time points (0, 3 and 8 hours) by using Agilent microarrays. Furthermore, a selected number of genes were confirmed by RT-qPCR. Gene signatures of stimulated DCs were obtained and genes involved in inflammatory process and T helper cell polarization were highly up regulated upon stimulation. Moreover, a set of 204 genes were statistically different between susceptible and resistant animals, and grouped them according to their predisposition to staphylococcal infection. Interestingly, a role of classical pathway of Complement and early regulation of inflammation is observed in the resistant line through over expression of C1q and Ido1 genes respectively. On the opposite, over expression of genes in the IL1R pathway in the susceptible animals was noticed. Furthermore, leucocyte extravasation pathway was also found dominant in the susceptible line. Conclusion/Significance: we successfully obtained Staphylococcus aureus associated gene expression of ovine BM-DC in 8 hour kinetics experiment. Distinct transcriptional profiles of dendritic cells obtained from resistant and susceptible lines may explain susceptibility towards S. aureus infections in a broad context. Keywords: Staphylococcus aureus, dendritic cells, mammalian, transcriptome, immunity, mastitis 44 sample records; two-colour dye-swap experimental design

Dataset Information

Genome-scale analysis of Staphylococcus aureus reveals host-specific diversification of the core genome.

Publications

Genome-wide analysis of ruminant Staphylococcus aureus reveals diversification of the core genome.

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