Project description:Neonatal meningitis caused by Escherichia coli (NMEC) is a leading cause of morbidity and mortality in newborns, and its pathogenesis relies on the ability of the bacterium to adapt and survive in diverse host environments. Despite advances in neonatal care, significant gaps remain in our understanding of how NMEC reprogram their transcriptome to survive in physiologically relevant niches. This study investigated the transcriptomic profiles of E. coli strain RS218 (O18:H7:K1) in four under host-relevant environment —colonic fluid (CF), serum (S), human brain endothelial cells (HBECs) and cerebrospinal fluid (CSF)—to mimic the infection landscape of neonatal meningitis. High-throughput RNA sequencing (RNA-seq) was performed to profile NMEC’s transcriptomic responses in each niche, and differential gene expression analyses were conducted to identify enriched pathways.
Project description:Preterm birth is currently the leading cause of neonatal morbidity and mortality. Genetic, immunological and infectious causes are suspected. Preterm infants have a higher risk of severe bacterial neonatal infections, most of which are caused by Escherichia coli an in particular E. coli K1strains. Women with history of preterm delivery have a high risk of recurrence and therefore constitute a target population for the development of vaccine against E. coli neonatal infections. Here, we characterized the immunological, microbiological and protective properties of a live attenuated vaccine candidate in adult female mice and their pups against after a challenge by K1 and non-K1 strains of E. coli. Our results show that the E. coli K1 E11 aroA vaccine induces strong immunity, driven by polyclonal bactericidal antibodies. In our model of meningitis, pups born to mothers immunized before mating were well protected against various K1 and non-K1 strains of E. coli. Given the very high mortality rate and the neurological sequalae associated with neonatal E. coli K1 meningitis, our results constitute preclinical proof of concept for the development of a live attenuated vaccine against severe E. coli infections in women at risk of preterm delivery.
Project description:Cronobacter (C.) is an important emerging opportunistic foodborne pathogen representing significant cause of mortality in neonatal patients with bacteremia and meningitis. Knowledge on the pathobiology of Cronobacter mediated meningitis has to a large extend been explored using in vitro models. To explore the innate immune response against the neonatal sepsis/meningitis causing isolate C. turicensis z3032 in vivo, zebrafish larvae (Danio rerio) were used as infection model. Following establishment of infection in zebrafish larvae with z3032, dual RNA-sequencing of host-pathogen was undertaken to profile RNA expression simultaneously in the pathogen and the head region of the zebrafish host.
Project description:Tuberculosis co-infected with HIV may increase the risk of causing meningitis. Tuberculous meningitis co-infected with HIV associated with high mortality and severe neurological abnormalities in affected individuals. We have carried out TBM co-infected with HIV gene expression study using whole human genome microarrays. We identified 796 differentially expressed genes with fold change cut off of 2 or more than 2. Out of 796 differentially expressed genes, 398 were upregulated and 396 were downregulated. We have validated two molecules from microarray data using immunohistochemistry. The proposed study carried out mRNA expression profiling of five samples from patients diagnosed with tuberculous meningitis coinfected with HIV and four head injury cases were used as controls. We have used 4X44K arrays from agilent platform. To validate our microarray results, we have done immunohistochemistry on 10 TBM+HIV cases and 10 control groups.
Project description:Tuberculosis co-infected with HIV may increase the risk of causing meningitis. Tuberculous meningitis co-infected with HIV associated with high mortality and severe neurological abnormalities in affected individuals. We have carried out TBM co-infected with HIV gene expression study using whole human genome microarrays. We identified 796 differentially expressed genes with fold change cut off of 2 or more than 2. Out of 796 differentially expressed genes, 398 were upregulated and 396 were downregulated. We have validated two molecules from microarray data using immunohistochemistry.