Project description:<p>In this study, we used admixture mapping to test the hypothesis that genomic variations with different frequencies in European and African ancestral genomes influence susceptibility to Staphylococcus aureus bacteremia (SAB) in a sample of African Americans. A total of 565 adult African Americans were genotyped for admixture mapping. Cases were unique African American adult inpatients with monomicrobial SAB (N=390) and controls are age-matched adult African American inpatients with no current or past S. aureus infection (N=175).</p> <p>After empirical multiplicity adjustment, one region on chromosome 6 (52 SNPs, P = 4.56e-05) in the HLA class II region was found to exhibit a genome-wide statistically significant increase in European ancestry. This region encodes genes involved in HLA-mediated immune response and these results provide additional evidence for genetic variation influencing HLA-mediated immunity, modulating susceptibility to SAB. </p>
Project description:Meatbolomics data from the manuscript Multi-omic Signatures of Host Response Associated with the Presence, Type, and Outcome of Enterococcal Bacteremia.
Project description:Focusing on host response to infection, we utilized a murine model to develop a blood gene expression signature that accurately classified mice with candidemia and distinguished candidemia from S. aureus bacteremia. Validation of the signature was achieved in an independent cohort of mice.
Project description:Meatbolomics data from the manuscript Multi-omic Signatures of Host Response Associated with the Presence, Type, and Outcome of Enterococcal Bacteremia.
Project description:Proteomics data from the manuscript Multi-omic Signatures of Host Response Associated with the Presence, Type, and Outcome of Enterococcal Bacteremia.
Project description:The factors that determine the outcome of clinical tuberculosis lie within both the host and the pathogen, Mycobacterium tuberculosis (Mtb). The advent of recombinant inbred mouse panels and next-generation transposon mutagenesis and sequencing approaches has enabled dissection of the host-pathogen interface for mammalian and pathogen genetic determinants of disease outcome. To identify host and pathogen genetic drivers of Mtb infection, we infected 19 genotypes from the BXD panel, bred from Mtb-resistant C57BL/6J (B6) and Mtb-susceptible DBA/2J (D2), with a comprehensive library of transposon mutants (TnSeq). The survival of each of the ~4000 bacterial mutants within each distinct host was quantified and leveraged as refined “endophenotypes”, directly reporting on the infection microenvironment. We leveraged QTL mapping to associate each varying bacterial fitness endophenotype to the host genome and identified 140 significant host-pathogen quantitative trait loci (hpQTL). This host-pathogen interaction screen reinforces the utility of bacterial mutant libraries as precise reporters of host immunological microenvironment during infection and highlights host gene candidates for further investigation.
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.
