Our research focuses on the pathogenesis of enteric bacterial pathogens, including Vibrio parahaemolytics, Vibrio cholerae, and Salmonella enterica spp. The emergence and spread o f multidrug-resistant bacteria are big problems these days. It is predicted that drug-resistant bacterial infection will bring about 10 million annual deaths by 2050. We believe that understanding detailed mechanisms of bacterial pathogenicity gives us a clue to the development of effective vaccines and establishment of new treatment strategies without antibiotics. We will promote our study with various approaches, such as global epidemic surveillances, in vivo animal infection models, and in vitro molecular biological analyses, and make maximum efforts to produce talented researchers who can play on a global stage through study and experience.
- Toshio Kodama
- Associate Professor
- Hirotaka Hiyoshi
- Assistant Professor
- Hiroyuki Terashima
- Yumiko Matsumoto
- Azusa Hiyoshi
- V. parahaemolyticus Pathogenesis
We have worked on V. parahaemolyticus for decades, and found that one set of Type III Secretion System (T3SS2) is necessary for induction of diarrhea in the patients infected with this pathogen. We have also identified and characterized effector proteins secreted from T3SS2, and revealed regulatory mechanisms of T3SS2-related genes. We recently demonstrated that an exotoxin, thermostable direct hemolysin (TDH), is secreted via T3SS2 in tandem with the Sec machinery, facilitates the distinct virulence traits. However, detailed mechanisms of how this pathogen colonizes the host intestine and induces diarrhea have remained unknown. We therefore try to understand a comprehensive mechanism of V. parahaemolyticus infection by generating a new murine infection model, dissecting the expression mechanism of T3SS2-related genes, determining 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 factor(s) that contributes to global dissemination and characterize its role in infection.
- Salmonella Pathogenesis
We are interested in Salmonella pathogenesis. A big goal in this project is to understand how S. enterica spp. cause systemic infection in immunocompetent humans for developing more effective vaccines and therapies without relying on antibiotics. The Type III Secretion System (T3SS) coded on Salmonella Pathogenicity Island 2 (SPI-2) is known as an essential virulence factor for establishing systemic infection and resisting the defense system of innate immune cells, such as macrophage and neutrophil, but its exact mechanism to disseminate into systemic sites in the host remains unknown. We have tried to uncover the mechanism, how S. enterica spp. cause systemic infection by dissecting the functions of the T3SS and its effector proteins using various approaches, including in Vivo mouse infection models, in Vitro biological assays, epidemic surveillance, and in silico genetic comparisons among different S. enterica serovars (i.e., Typhimurium, Typhi, and Paratyphi A).
Recent main research achievement
- Hiyoshi et al. Cell Host Microbe 2022;30(2):163-170.
- Nishikino et al. J Biochem 2022;171(4):443-450.
- Terashima et al. Sci Rep 2022;12(1):2979.
- Al Kadi et al. mSystems 2021;6(6):e0099621.
- Prithvisagar et al. Virulence 2021;12(1):1936-1949.