RRC ID 59284
Author Nguyen AQ, Shimohata T, Hatayama S, Tentaku A, Kido J, Bui TMH, Uebanso T, Mawatari K, Takahashi A.
Title Type III Secretion Effector VopQ of Vibrio parahaemolyticus Modulates Central Carbon Metabolism in Epithelial Cells.
Journal mSphere
Abstract Vibrio parahaemolyticus is a Gram-negative halophilic pathogen that frequently causes acute gastroenteritis and occasional wound infection. V. parahaemolyticus contains several virulence factors, including type III secretion systems (T3SSs) and thermostable direct hemolysin (TDH). In particular, T3SS1 is a potent cytotoxic inducer, and T3SS2 is essential for causing acute gastroenteritis. Although much is known about manipulation of host signaling transductions by the V. parahaemolyticus effector, little is known about the host metabolomic changes modulated by V. parahaemolyticus To address this knowledge gap, we performed a metabolomic analysis of the epithelial cells during V. parahaemolyticus infection using capillary electrophoresis-time of flight mass spectrometry (CE-TOF/MS). Our results revealed significant metabolomic perturbations upon V. parahaemolyticus infection. Moreover, we identified that T3SS1's VopQ effector was responsible for inducing the significant metabolic changes in the infected cells. The VopQ effector dramatically altered the host cell's glycolytic, tricarboxylic acid cycle (TCA), and amino acid metabolisms. VopQ effector disrupted host cell redox homeostasis by depleting cellular glutathione and subsequently increasing the level of reactive oxygen species (ROS) production.IMPORTANCE The metabolic response of host cells upon infection is pathogen specific, and infection-induced host metabolic reprogramming may have beneficial effects on the proliferation of pathogens. V. parahaemolyticus contains a range of virulence factors to manipulate host signaling pathways and metabolic processes. In this study, we identified that the T3SS1 VopQ effector rewrites host metabolism in conjunction with the inflammation and cell death processes. Understanding how VopQ reprograms host cell metabolism during the infection could help us to identify novel therapeutic strategies to enhance the survival of host cells during V. parahaemolyticus infection.
Volume 5(2)
Published 2020-3-18
DOI 10.1128/mSphere.00960-19
PII 5/2/e00960-19
PMID 32188755
PMC PMC7082145
MeSH Bacterial Proteins / genetics Bacterial Proteins / metabolism* Caco-2 Cells Carbon / metabolism* Cell Death Cell Line Epithelial Cells / metabolism* Gene Expression Regulation, Bacterial Host-Pathogen Interactions Humans Metabolomics Type III Secretion Systems / genetics Type III Secretion Systems / metabolism* Vibrio parahaemolyticus / genetics* Vibrio parahaemolyticus / metabolism Virulence Factors
IF 4.447
Times Cited 0
Pathogenic bacteria Vibrio parahaemolyticus RIMD 2210633