The objective of this department is to understand the molecular mechanisms by which pathogenic bacterial virulence factors affect host cell functions. Our present research interests include:
(1) Analysis of the structure and function of bacterial protein toxins
Bacterial protein toxins, which are the most poisonous substances on the earth, act specifically on a particular cell or biomolecule. To understand how bacterial toxins act so powerfully and specifically, we are analyzing their effects on the host at the systemic, tissue, cellular and molecular levels. The toxins currently under investigation include Bordetella dermonecrotic toxin, Pasteurella toxin, Clostridium perfringens enterotoxin, and Escherichia coli cytotoxic necrotizing factor. We are also analyzing the steric structure and molecular localization of the functional domains of these toxins. Together, these approaches will help to clarify the structure and function of these bacterial toxins.
(2) Analysis of the pathogenesis of whooping cough
Bordetella pertussis, is a bacterial pathogen that infects the human respiratory tract and causes whooping cough, which is characterized by paroxysmal cough. Two important questions remain in terms of the pathogenesis of B. pertussis infection: Why does B. pertussis infect humans but not other mammals? How does the bacteria cause the paroxysmal cough? We are examining the pathology of the disease and function of bacterial virulence factors using an animal model of the infection.
Fig. 1: Bacterial protein toxins with various activities that influence particular cellular functions.
Many bacterial protein toxins exert their toxicity by modifying important functions of the host cells. The relevant physiological functions of the cells can be determined by dissecting the actions of the bacterial toxins.
Fig. 2: Overall structure of Clostidium perfringens enterotoxin
Fig. 3: B. pertussis, B. parapertussis, and B. bronchiseptica are closely related pathogenic bacteria. B. bronchiseptica with the largest genome shows the broadest host range, whereas B. pertussis with the smallest genome shows the narrowest range. B. pertussis is believed to have evolved from a lineage of B. bronchiseptica through deletion and/or translocation of a large number of genes.