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Vibrio survives by rewiring host cell signaling
Vibrio parahaemolyticus (V. para) is a major cause of food poisoning caused by eating raw or undercooked shellfish. Like other types of bacteria, V. para delivers effectors into host cells through type 3 secretion systems (T3SSs). Those delivered through T3SS1 cause nonapoptotic death in various cultured cells. De Nisco et al. analyzed the transcriptional response of primary human fibroblasts to infection with a strain of V. para that has an intact T3SS1, which enables the bacterium to survive in its natural habitat, but lacks T3SS2, which mediates gastroenteritis in humans. V. para T3SS1 induced a rapid, dynamic transcriptional response that initially suppressed cell death and stimulated cell survival networks. Later in infection, effectors delivered through T3SS1 inhibited prosurvival signaling posttranslationally and induced cell death.
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.