Project description:Staphylococcus hominis is frequently isolated from human skin and we hypothesize that it may protect the cutaneous barrier from opportunistic pathogens. We determined that S. hominis makes six unique auto inducing peptide (AIP) signals that inhibit the major virulence factor accessory gene regulator (agr) quorum sensing system of Staphylococcus aureus. We solved and confirmed the structures of three novel AIP signals in conditioned media by mass spectrometry, then validated synthetic AIP activity against all S. aureus agr classes. Synthetic AIPs also inhibited the conserved agr system in a related species, Staphylococcus epidermidis. We determined the distribution of S. hominis agr types on healthy human skin and found S. hominis agr-I and agr-II were highly represented across subjects. Further, synthetic AIP-II was protective in vivo against S. aureus-associated dermonecrotic or epicutaneous injury. Together, these findings demonstrate that a ubiquitous colonizer of human skin has a fundamentally protective role against opportunistic damage.
Project description: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
Project description: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.
Project description:This analysis is part of the study Whole-transcriptome analysis of Staphylococcus aureus under laboratory and infection-mimicking conditions (Mäder, Nicolas et al., to be submitted) where the S. aureus HG001 transcriptome was analyzed under more than 40 different bilogical conditions. Genomic DNA was prepared from four independent cultures of S. aureus HG001 cells; after sonication, DNA was labeled with Cy3 and hybridized to tiling arrays. The data are used in transcriptome studies to compute expression intensities from raw intensity data using a model of shift and drift. genomic DNA from wild type
Project description:This analysis is part of the study Whole-transcriptome analysis of Staphylococcus aureus under laboratory and infection-mimicking conditions (Mäder, Nicolas et al., to be submitted) where the S. aureus HG001 transcriptome was analyzed under more than 40 different bilogical conditions. Genomic DNA was prepared from four independent cultures of S. aureus HG001 cells; after sonication, DNA was labeled with Cy3 and hybridized to tiling arrays. The data are used in transcriptome studies to compute expression intensities from raw intensity data using a model of shift and drift.