Project description:The pore-forming protein gasdermin D (GSDMD) executes lytic cell death called pyroptosis to eliminate the replicative niche of intracellular pathogens. Evolution favors pathogens that circumvent this host defense mechanism. Here, we show that the Shigella ubiquitin ligase IpaH7.8 functions as an inhibitor of GSDMD. Shigella is an enteroinvasive bacterium that causes hemorrhagic gastroenteritis in primates, but not rodents. IpaH7.8 contributes to species specificity by ubiquitinating human, but not mouse, GSDMD and targeting it for proteasomal degradation. Accordingly, infection of human epithelial cells with IpaH7.8-deficient Shigella flexneri results in increased GSDMD-dependent cell death compared with wild type. Consistent with pyroptosis contributing to murine disease resistance, eliminating GSDMD from NLRC4-deficient mice, which are already sensitized to oral infection with Shigella flexneri, leads to further enhanced bacterial replication and increased disease severity. This work highlights a species-specific pathogen arms race focused on maintenance of host cell viability.
Project description:Non-typhoidal Salmonella serotypes (NTS) cause a self-limited gastroenteritis while pediatric patients with severe Plasmodium falciparum malaria can develop a life threatening bacteremia that is a major source of child mortality in sub-Saharan Africa. We used microarrays to detail genome-scale gene expression profiles underlying gastrointestinal immune responses to bacterial infection in mice
Project description:Cardioviruses are a genus of picornaviruses that cause severe illnesses in rodents, but little is known about the prevalence, diversity, or spectrum of disease of such agents among humans. We report the identification of a group of human cardioviruses that have been detected and cloned directly from patient specimens (Chiu and DeRisi, et al, PNAS, 2008). This series includes 9 arrays (both raw and normalized data) used to detect cardioviruses in human respiratory and stool specimens. The arrays employed here are capable of pan-viral detection (Wang and DeRisi, et al., PNAS, 2002). Keywords: viral detection, cardiovirus, TMEV, gastroenteritis
Project description:Noroviruses have been widely recognized for their importance as causative agents of non-bacterial gastroenteritis. Mouse norovirus is the only representative of the norovirus genus, family Caliciviridae, able to grow in cell culture. The aim of this study is to describe the differences in the expression profiles of MNV-1 and mock-infected macrophages (RAW 264.7 cells), in order to better understand the response of the host cell to norovirus infection.
Project description:Vibrio parahaemolyticus is the leading bacterial cause for seafood-related gastroenteritis worldwide. As an intestinal pathogen, V. parahaemolyticus competes with other commensal bacteria for the same pool of nutrients. The major source of nutrition for intestinal bacteria is intestinal mucus. We wanted to determine the expression profile of wild-type V. parahaemolyticus in mouse intestinal mucus and then perform a differential expression analysis in a ∆rpoN deletion mutant.
Project description:Cardioviruses are a genus of picornaviruses that cause severe illnesses in rodents, but little is known about the prevalence, diversity, or spectrum of disease of such agents among humans. We report the identification of a group of human cardioviruses that have been detected and cloned directly from patient specimens (Chiu and DeRisi, et al, PNAS, 2008). This series includes 9 arrays (both raw and normalized data) used to detect cardioviruses in human respiratory and stool specimens. The arrays employed here are capable of pan-viral detection (Wang and DeRisi, et al., PNAS, 2002). Keywords: viral detection, cardiovirus, TMEV, gastroenteritis The series includes 3 arrays from respiratory samples and 6 arrays from stool samples. Among the 3 arrays from respiratory sample, 1 array has a signature for an adenovirus, 1 array has a signature for human metapneumovirus, and 1 array has a signature for cardiovirus UC1 (see Chiu and DeRisi, et al., PNAS, in 2008). All 6 arrays from stool samples are cardiovirus-positive; some show evidence of dual infection with other gastroenteritis viruses (i.e. norovirus, rotavirus, etc.). Data in Sample records fed to E-Predict (Urisman, et al, Genome Biology, 2005) E-Predict normalization metrics Array Normalization: Sum E-Matrix Normalization: Quadratic Distance Metric: Pearson Uncentered
Project description:Non-typhoidal Salmonella serotypes (NTS) cause a self-limited gastroenteritis while pediatric patients with severe Plasmodium falciparum malaria can develop a life threatening bacteremia that is a major source of child mortality in sub-Saharan Africa. We used microarrays to detail genome-scale gene expression profiles underlying gastrointestinal immune responses to bacterial infection in mice Responses were measured in mouse cecal mucosa to infection of non-typhodal Salmonella and Plasmodium yoelii, both singularly and in combination.