RRC ID 53198
Author De Nisco NJ, Kanchwala M, Li P, Fernandez J, Xing C, Orth K.
Title The cytotoxic type 3 secretion system 1 of Vibrio rewires host gene expression to subvert cell death and activate cell survival pathways.
Journal Sci Signal
Abstract Bacterial effectors potently manipulate host signaling pathways. The marine bacterium Vibrio parahaemolyticus (V. para) delivers effectors into host cells through two type 3 secretion systems (T3SSs). T3SS1 is vital for V. para survival in the environment, whereas T3SS2 causes acute gastroenteritis in human hosts. Although the natural host is undefined, T3SS1 effectors attack highly conserved cellular processes and pathways to orchestrate nonapoptotic cell death. To understand how the concerted action of T3SS1 effectors globally affects host cell signaling, we compared gene expression changes over time in primary fibroblasts infected with V. para that have a functional T3SS1 (T3SS1+) to those in cells infected with V. para lacking T3SS1 (T3SS1-). Overall, the host transcriptional response to both T3SS1+ and T3SS1-V. para was rapid, robust, and temporally dynamic. T3SS1 rewired host gene expression by specifically altering the expression of 398 genes. Although T3SS1 effectors targeted host cells at the posttranslational level to cause cytotoxicity, V. para T3SS1 also precipitated a host transcriptional response that initially activated cell survival and repressed cell death networks. The increased expression of several key prosurvival transcripts mediated by T3SS1 depended on a host signaling pathway that is silenced posttranslationally later in infection. Together, our analysis reveals a complex interplay between the roles of T3SS1 as both a transcriptional and posttranslational manipulator of host cell signaling.
Volume 10(479)
Published 2017-5-16
DOI 10.1126/scisignal.aal4501
PII 10/479/eaal4501
PMID 28512145
PMC PMC5662193
MeSH Animals Autophagy / physiology Bacterial Proteins / genetics Bacterial Proteins / metabolism* Bacterial Toxins / metabolism* Cell Survival / genetics Gene Expression* Gene Expression Profiling Genome-Wide Association Study HeLa Cells Host-Pathogen Interactions / genetics* Humans Mice Primary Cell Culture RAW 264.7 Cells RNA / genetics Type III Secretion Systems / metabolism* Vibrio Infections / genetics* Vibrio Infections / microbiology* Vibrio parahaemolyticus / genetics Vibrio parahaemolyticus / metabolism Vibrio parahaemolyticus / pathogenicity* rho GTP-Binding Proteins / metabolism
IF 6.565
Pathogenic bacteria 病原細菌