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Published on: October 13, 2015
The Vibrio parahaemolyticus Type III Secretion Systems manipulate host cell MAPK for critical steps in pathogenesis
Ksenia Matlawska-Wasowska1, Rebecca Finn, Ana Mustel
1Discipline of Microbiology, School of Natural Sciences, National University of Ireland, Galway, University Road, Galway, Ireland.
Background:
Vibrio parahaemolyticus is a food-borne pathogen causing inflammation of the gastrointestinal epithelium. Pathogenic strains of this bacterium possess two Type III Secretion Systems (TTSS) that deliver effector proteins into host cells. In order to better understand human host cell responses to V. parahaemolyticus, the modulation of Mitogen Activated Protein Kinase (MAPK) activation in epithelial cells by an O3:K6 clinical isolate, RIMD2210633, was investigated. The importance of MAPK activation for the ability of the bacterium to be cytotoxic and to induce secretion of Interleukin-8 (IL-8) was determined.
Results:
V. parahaemolyticus deployed its TTSS1 to induce activation of the JNK, p38 and ERK MAPK in human epithelial cells. VP1680 was identified as the TTSS1 effector protein responsible for MAPK activation in Caco-2 cells and the activation of JNK and ERK by this protein was important in induction of host cell death. V. parahaemolyticus actively induced IL-8 secretion in a response mediated by TTSS1. A role for VP1680 and for the ERK signalling pathway in the stimulation of IL-8 production in epithelial cells by V. parahaemolyticus was established. Interestingly, TTSS2 inhibited IL-8 mRNA transcription at early stages of interaction between the bacterium and the cell.
Conclusions:
This study demonstrated that V. parahaemolyticus activates the three major MAPK signalling pathways in intestinal epithelial cells in a TTSS1-dependent manner that involves the TTSS1 effector VP1680. Furthermore VP1680 and JNK and ERK activation were needed for maximal cytotoxicity of the bacterium. It was shown that V. parahaemolyticus is a strong inducer of IL-8 secretion and that induction reflects a balance between the effects of TTSS1 and TTSS2. Increases in IL-8 secretion were mediated by TTSS1 and VP1680, and augmented by ERK activation. These results shed light on the mechanisms of bacterial pathogenesis mediated by TTSS and suggest significant roles for MAPK signalling during infection with V. parahaemolyticus.
Insights
Vibrio parahaemolyticus uses its Type III Secretion System 1 (TTSS1) to activate MAPK pathways, leading to host cell death and IL-8 secretion. TTSS1 effector VP1680 and MAPK activation are crucial for these pathogenic effects.
Area of Science:
- Microbiology
- Cell Biology
- Immunology
Background:
- Vibrio parahaemolyticus is a foodborne pathogen that causes gastrointestinal inflammation.
- Pathogenic strains utilize Type III Secretion Systems (TTSS) to deliver effector proteins into host cells.
- Understanding host cell responses, particularly Mitogen Activated Protein Kinase (MAPK) activation, is crucial for V. parahaemolyticus pathogenesis.
Purpose of the Study:
- To investigate the modulation of MAPK activation in epithelial cells by V. parahaemolyticus.
- To determine the role of MAPK activation in bacterial cytotoxicity and Interleukin-8 (IL-8) secretion.
- To elucidate the specific TTSS effectors involved in these host cell responses.
Main Methods:
- Utilized Caco-2 epithelial cells and a V. parahaemolyticus O3:K6 clinical isolate (RIMD2210633).
- Investigated MAPK (JNK, p38, ERK) activation in response to bacterial infection.
- Identified TTSS effector proteins responsible for MAPK modulation and assessed their role in host cell death and IL-8 production.
Main Results:
- V. parahaemolyticus TTSS1 induced JNK, p38, and ERK MAPK activation.
- TTSS1 effector VP1680 was identified as a key mediator of MAPK activation and host cell death.
- TTSS1 promoted IL-8 secretion, while TTSS2 inhibited IL-8 mRNA transcription early in infection.
- VP1680 and ERK signaling were essential for V. parahaemolyticus-induced IL-8 production.
Conclusions:
- V. parahaemolyticus activates MAPK signaling via TTSS1 and effector VP1680, contributing to pathogenesis.
- VP1680 and MAPK activation (JNK, ERK) are critical for V. parahaemolyticus cytotoxicity.
- Bacterial induction of IL-8 secretion is a complex process involving a balance between TTSS1 and TTSS2 activities.
- MAPK signaling plays a significant role in the host-pathogen interactions during V. parahaemolyticus infection.
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