Project description:Macrophages provide a crucial environment for Salmonella enterica serovar Typhi (S. Typhi) to multiply during typhoid fever, yet our understanding of how human macrophages and S. Typhi interact remains limited. In this study, we delve into the dynamics of S. Typhi replication within human macrophages and the resulting heterogeneous transcriptomic responses of macrophages during infection. Our study reveals key factors that influence macrophage diversity, uncovering distinct immune and metabolic pathways associated with different stages of S. Typhi intracellular replication in macrophages. Of note, we found that macrophages harboring replicating S. Typhi are skewed towards an M1 pro-inflammatory state, whereas macrophages containing non-replicating S. Typhi exhibit neither a distinct M1 pro-inflammatory nor M2 anti-inflammatory state. Additionally, macrophages with replicating S. Typhi were characterized by the increased expression of genes associated with STAT3 phosphorylation and the activation of the STAT3 transcription factor. Our results shed light on transcriptomic pathways involved in the susceptibility of human macrophages to intracellular S. Typhi replication, thereby providing crucial insight into host phenotypes that restrict and support S. Typhi infection.
Project description:FabR ChIP-chip on Salmonella enterica subsp. enterica serovar Typhimurium SL1344 using anti-Myc antibody against strain with chromosomally 9Myc-tagged FabR (IP samples) and wildtype strain (mock IP samples)
Project description:Investigation of whole genome gene expression level changes in a Salmonella enterica serovar Typhimurium 14028 delta GidA mutant The mutant described in this study is further analyzed in Shippy, D. C., N. M. Eakley, P. N. Bochsler, and A. A. Fadl. 2011. Biological and virulence characteristics of Salmonella enterica serovar Typhimurium following deletion of glucose-inhibited division (gidA) gene. Microb Pathog.
Project description:Investigation of whole genome gene expression level changes in a Salmonella enterica serovar Typhimurium UK1 delta-iacP mutant, compared to the wild-type strain. IacP is resoponsible for the secretion of virulence effector proteins via the type III secretion system, thereby contributing the virulence of S. Typhimurium. The mutants analyzed in this study are further described in Kim et al. 2011. Role of Salmonella Pathogenicity Island 1 Protein IacP in Salmonella enterica Serovar Typhimurium Pathogenesis. Infection and Immunity 79(4):1440-1450 (PMID 21263021).
Project description:Infection with Salmonella enterica serovar Typhi in humans causes the systemic, life-threatening disease typhoid fever. In the laboratory, typhoid fever can be modeled through the inoculation of susceptible mice with Salmonella enterica serovar Typhimurium. The ensuing disease is characterized by systemic dissemination and colonization of many organs, including the liver, spleen and gallbladder. Using this murine model, we previously characterized the interactions between Salmonella Typhimurium and host cells in the gallbladder and showed that this pathogen can successfully invade gallbladder epithelial cells and proliferate. Additionally, we showed that Salmonella Typhimurium can use bile phospholipids to grow at high rates. These abilities are likely important for quick colonization of the gallbladder during typhoid fever and further pathogen dissemination through fecal shedding. To further characterize the interactions between Salmonella and the gallbladder environment we compared the transcriptome of Salmonella cultures grown in LB or physiological murine bile. Our data showed that many genes involved in bacterial central metabolism are affected by bile, with the citric acid cycle being repressed and alternative respiratory systems being activated. Additionally, our study revealed a new aspect of Salmonella interactions with bile through the identification of phoP as a bile-responsive gene. Repression of phoP expression does not involve PhoPQ sensing of a bile component. Due to its critical role in Salmonella virulence, further studies in this area will likely reveal aspects of the interaction between Salmonella and bile that are relevant to disease.
Project description:Investigation of whole genome gene expression level changes in a Salmonella enterica serovar Typhimurium UK1 delta-iacP mutant, compared to the wild-type strain. IacP is resoponsible for the secretion of virulence effector proteins via the type III secretion system, thereby contributing the virulence of S. Typhimurium. The mutants analyzed in this study are further described in Kim et al. 2011. Role of Salmonella Pathogenicity Island 1 Protein IacP in Salmonella enterica Serovar Typhimurium Pathogenesis. Infection and Immunity 79(4):1440-1450 (PMID 21263021). A chip study using total RNA recovered from two separate wild-type cultures of Salmonella enterica serovar Typhimurium UK1 and two separate cultures of a mutant strain, Salmonella enterica serovar Typhimurium UK1 delta-iacP. Each chip measures the expression level of 4,302 genes from Salmonella enterica serovar Typhimurium.
Project description:Investigation of whole genome gene expression level changes in a Salmonella enterica serovar Typhimurium 14028 delta GidA mutant The mutant described in this study is further analyzed in Shippy, D. C., N. M. Eakley, P. N. Bochsler, and A. A. Fadl. 2011. Biological and virulence characteristics of Salmonella enterica serovar Typhimurium following deletion of glucose-inhibited division (gidA) gene. Microb Pathog. A single chip study using three separate cultures of wild-type Salmonella enterica serovar Typhimurium 14028 and three separate cultures of a single mutant, delta GidA Salmonella enterica serovar Typhimurium 14028.