Cytotoxic Vibrio T3SS1 Rewires Host Gene Expression to Subvert Cell Death Signaling and Activate Cell Survival Networks

ABSTRACT: Abstract: The type three secretion system 1 (T3SS1) of the marine bacterium, Vibrio parahaemolyticus, orchestrates a host cell death comprised of distinct stages defined by the action of specific effectors. To understand how the host responds to the T3SS1, we analyzed gene expression changes over time in infected primary fibroblasts by RNA-seq. The host cell’s transcriptional response was rapid, robust and temporally distinct. Despite the lethal action of the T3SS1 effectors, network analysis indicated that the integrated host transcriptional response to T3SS1 effectors activated cell survival and repressed cell death networks, suggesting that T3SS1 masks its cytotoxicity to the host cell. Pathway analysis revealed that signaling through several pathways, including MAPK pathways, was specifically altered by T3SS1. Overall, this temporal analysis of T3SS1-mediated subversion of host cell signaling revealed cytoprotective pathways that are likely hijacked by many bacterial pathogens to ensure survival. Methods: We employed genome-wide transcriptional profiling methods (RNA-seq) to measure changes in gene expression over time in response to infection with POR4:T3SS1- or POR3:T3SS1+. Time points were collected 45, 60, 75 and 90 minutes post-infection. In total, libraries from 27 samples (triplicates of uninfected, POR3/4 at t=45, 60, 75, and 90 minutes) were sequenced and mapped to the human genome. EdgeR was used for differential expression analysis using statistical cutoffs of of false discovery rate (FDR) ≤0.01, log2counts-per-million (log2CPM) ≥0 and fold change (FC) cutoffs of -1.5≥ FC ≥1.5

ORGANISM(S): Homo sapiens

PROVIDER: GSE93783 | GEO | 2017/04/28

SECONDARY ACCESSION(S): PRJNA362363

REPOSITORIES: GEO