ABSTRACT: Genomic analysis of sequential outbreaks of Burkholderia cepacia and multi-drug resistant extended spectrum beta-lactamase producing Klebsiella species in a West African tertiary hospital neonatal unit
Project description:Burkholderia cenocepacia J2315 belongs to the ET12 lineage which has caused outbreaks among cystic fibrosis patients worldwide. Strains belonging to the ET12 lineage are characterized by the presence of the “Burkholderia cepacia epidemic strain marker” (BCESM). This marker is located on a genomic island involved in virulence, but the exact function of many genes in the BCESM region remains unknown. In the present study we investigated the function of three of these genes (BCAM0257, BCAM0258 and BCAM0259). We created overexpression mutants and performed a transcriptome analysis of the toxin (BCAM0258) overexpression mutant.
Project description:Extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae: Insights from a tertiary hospital in Southern Thailand
Project description:Studies in specific pathogen-free mice revealed that naïve T (Tn) cells require two homeostatic signals for long-term survival–the sub-threshold T cell receptor:self-peptide–MHC contact, and IL-7 stimulation. It is not known how microbial exposure impacts Tn homeostasis. We report that the presence of infections led to expansion of a novel subpopulation of long-lived, Ly6C+ Tn cells with rapid effector function. Monoinfection with West Nile virus transiently, and polymicrobial exposure persistently, enhanced Ly6C expression on CD5hi cells, the latter yielding a numerical Tn cell increase in the lymph nodes. Conversion and expansion of Ly6C+ Tn cells depended on IFN-I, that upregulated MHC class I expression and enhanced trophic TCR signaling in Tn cells. IFN-I-mediated signals extended lifespan, optimized homing to secondary and tertiary sites, and drove Ly6C+ Tn cells to higher “combat readiness” as judged by increased effector differentiation. Thereby, infection-driven IFN-I powerfully modulates Tn homeostasis and function.
Project description:The present study examines changes in global gene expression patterns and in virulence factor-associated genes in an extended spectrum beta-lactamase (ESBL)-producing UPEC (ESBL019) during the morphologic transitions induced by an ineffective antibiotic and in the presence of human primary bladder epithelial cells. The morphological shifts induced by ineffective antibiotics are associated with significant transcriptional virulence alterations in ESBL-producing UPEC, which may affect survival and persistence in the urinary tract.
Project description:Patient age 45 year old and above who presented with rectal bleeding at three tertiary hospitals in South West Nigeria were invited for colonoscopy. The clinical information of the patients and the colonoscopy data were analyzed
Project description:Episodic Ebola virus (EBOV) outbreaks, such as the current one in West Africa, emphasize the critical need for novel antivirals against this highly pathogenic virus. Here, we demonstrate that interferon gamma (IFNγ) prevents morbidity and mortality associated with EBOV infection when administered to mice either 24 hours prior to or 2 hours following EBOV infection. Microarray studies with IFNγ-stimulated human macrophages identified novel interferon-stimulated genes (ISGs) that inhibit EBOV infection upon ectopic expression. IFNγ treatment reduced viral RNA levels in macrophages to a similar degree as cells treated with the protein synthesis inhibitor, cycloheximide, suggesting that IFNγ treatment inhibits genome replication. As IFNγ treatment robustly protects mice against EBOV infection, we propose that this FDA-approved drug may serve as a useful prophylactic or therapeutic strategy during EBOV outbreaks, contributing to the currently limited arsenal of filovirus antivirals.
Project description:Episodic Ebola virus (EBOV) outbreaks, such as the current one in West Africa, emphasize the critical need for novel antivirals against this highly pathogenic virus. Here, we demonstrate that interferon gamma (IFNγ) prevents morbidity and mortality associated with EBOV infection when administered to mice either 24 hours prior to or 2 hours following EBOV infection. Microarray studies with IFNγ-stimulated human macrophages identified novel interferon-stimulated genes (ISGs) that inhibit EBOV infection upon ectopic expression. IFNγ treatment reduced viral RNA levels in macrophages to a similar degree as cells treated with the protein synthesis inhibitor, cycloheximide, suggesting that IFNγ treatment inhibits genome replication. As IFNγ treatment robustly protects mice against EBOV infection, we propose that this FDA-approved drug may serve as a useful prophylactic or therapeutic strategy during EBOV outbreaks, contributing to the currently limited arsenal of filovirus antivirals.
