Project description:Young adult fer-15;fem-1 Caenorhabditis elegans were infected with Staphylococcus aureus for 8 h to determine the transcriptional host response to Staphylococcus aureus. Analysis of differential gene expression in C. elegans young adults exposed to two different bacteria: E. coli strain OP50 (control), wild-type Staphylococcus aureus RN6390. Samples were analyzed at 8 hours after exposure to the different bacteria. These studies identified C. elegans genes induced by pathogen infection. Keywords: response to pathogen infection, innate immunity, host-pathogen interactions
Project description:We analysed the gene expression profiles after infection of Staphylococcus aureus at ZT4 in CXCL14-KO mice. The group of genes categolized as GO defense response (GO: 006952) were upregulated upon a response to Staphylococcus aureus infection. The expression of IL1b, Cxcl2, and Ccl3 were significantly suppressed in infected ear of Cxcl14-KO compared to that of WT.
Project description:In this study we investigated the transcriptional responses of keratinocyte-derived IκBζ (encoded by NFKBIZ) upon infection with the pathogenic Staphylococcus aureus (S. aureus) USA300 wildtype strain.
Project description:Analysis of transcriptional profiles in whole blood from patients with Staphylococcus aureus infection. The hypothesis tested is that transcriptional profile heterogeneity will reflect patient clinical heterogeneity.
Project description:Infection in diabetic foot ulcers (DFU) are one of the major complications associated with diabetic patients. Staphylococcus aureus is the most common offending pathogen in patients with infected DFU. Previous studies have suggested application of species-specific antibodies against S. aureus for diagnosis and monitoring treatment response. Early and accurate identification of the main pathogen is critical for management of DFU infection. Understanding the host immune response against species-specific infection may facilitate diagnosis and suggest potential intervention options to promote healing infected DFUs. We sought to investigate evolving host transcriptome associated with surgical treatment of S. aureus infected DFU. This study compared the transcriptome profile of twenty-one patients with S. aureus infected DFU who underwent initial foot salvage therapy with irrigation and debridement followed by intravenous antibiotics therapy. Blood samples were collected at the recruitment (0-weeks) and 8-week after therapy to isolate peripheral blood mononuclear cells (PBMC). We analyzed the PBMCs expression of transcriptomes at two different time points (0 vs 8-week). Subjects were further divided into two groups at 8-week: healed (n=17, 80.95%) versus non-healed (n=4,19.05%) based on the wound healing status. DESeq2 differential gene analysis was performed. An increased expression of IGHG1, IGHG2, IGHG3 and IGLV3-21, IGLV6-57 were noted during active infection at 0-week compared to 8-week. Lysine and arginine-rich histones (HIST1H2AJ, HIST1H2AL, HIST1H2BM, HIST1H3B and HIST1H3G) were upregulated at the initial phase of active infection at 0-week. CD177 and RRM2 were also upregulated at the initial phase of active infection (0-week) compared to 8-week follow-up. Genes of heat shock protein members (HSPA1A, HSPE1, and HSP90B1) were high in not-healed compared to healed patients 8-week after therapy. The outcome of our study suggests that identification of genes evolution based on a transcriptomic profiling could be a useful tool for diagnosing infection, assessing severity and assess host-immune response to therapies.
Project description:Therapy of Staphylococcus aureus bacteremia is often ineffective, even under optimal conditions, and adapted subclones with attenuated agr-mediated virulence activation are associated with persistent infection and mortality. To understand how apparent loss of virulence leads to increased mortality, we sequenced complete genomes from clone pairs from colonizing and infected sites of patients in whom S. aureus demonstrated a within-host downshift in agr function in the infecting isolate. Clone pairs with a downshift in agr function showed substantial genetic divergence compared to wild-type pairs from controls. Complementation studies further identified an agr-defective bacteremic strain that was highly virulent in vivo, which we linked to a mutation that restored expression of the agr-regulated ess/Type-VII secretion system; a known virulence factor. Our results suggest that selection pressure during invasive infection is strong enough to mutationally bypass agr-deficiency associated loss of virulence, and that efforts to suppress agr function may need to be reconsidered.