Activities

• V. parahaemolyticus Pathogenesis
  We have worked on V. parahaemolyticus for decades and found that a Type III Secretion System (T3SS2) is necessary for t he i nduction of diarrhea in patients infected with this pathogen (Hiyoshi et al., Infect Immune, 2010). We also identified and characterized effector proteins secreted from T3SS2 (Kodama et al., Cell Microbiol, 2007; Hiyoshi et al., Cell Host Microbe, 2011; Hiyoshi et al., PLoS Pathog, 2015) and revealed the regulatory mechanisms of T3SS2-related genes (Kodama et al., PLoS One, 2010; Gotoh et al., PLoS One, 2011; Tandhavanant et al., mBio, 2018). We recently demonstrated that an exotoxin, thermostable direct hemolysin (TDH), is secreted via T3SS2 in tandem with Sec machinery, facilitating distinct virulence traits (Matsuda et al., Nat Microbiol, 2019). However, the detailed mechanisms by which this pathogen colonizes the host intestine and induces diarrhea remain unknown. Therefore, we aimed to understand the comprehensive mechanism of V. parahaemolyticus infection by generating a new animal infection model, dissecting the expression mechanism of T3SS2-related genes, determining the biological activities of T3SS2 effectors, analyzing the interaction of microbiota, and other multidimensional approaches.
• Endemic Stains of Vibrio spp.
  We are planning to isolate Vibrio spp., including V. parahaemolyticus and V. cholerae, from patients, seafood, and environmental samples in endemic areas to elucidate the genetic characteristics and dynamics of epidemic strains. We will also try to determine the factors that contribute to global dissemination and characterize their role in infection.
• Salmonella Pathogenesis
  　We are interested in and analyzed the pathogenesis of Salmonella infections (Hiyoshi et al., Cell Rep, 2018; Hiyoshi et al., Cell Host Microbe, 2022; Zhang et al., mBio, 2022). A major goal of this project is to understand how S. enterica spp. causes systemic infection in humans to develop more effective vaccines and therapies without relying on antibiotics. Type III Secretion System (T3SS) encoded on Salmonella Pathogenicity Island 2 (SPI-2) is well known as an essential virulence factor for establishing systemic infection and resisting the host innate immune defense system mediated by macrophages and neutrophils. To uncover the mechanism by which S. enterica spp. causes systemic infection using T3SS, we attempt to dissect the functions of the T3SS in systemic infection and its effector proteins using various approaches, including in vivo mouse infection models, in vitro biological assays, single-cell RNA-sequencing, epidemic surveillance, and in silico genetic comparisons among different S. enterica serovars (i.e., Typhimurium, Typhi, and Paratyphi A).