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, are known to act specifically on a particular cell and a particular 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 are 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 the toxins. These approaches together will help to clarify the structure and function of these bacterial toxins.
(2) Analysis of the pathogenesis of whooping cough
Bordetella pertussis, a pathogenic bacterium, infects the human respiratory tract and causes whooping cough, which is characterized by paroxysmal cough. There are two significant questions about the pathogenesis of B. pertussis infection. First, why does B. pertussis only infect humans but not other mammals? Second, how do the bacteria cause the paroxysmal cough? We are examining the pathology of the disease and the function of bacterial virulence factors by 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: Bordetella pertussis, B. parapertussis, and B. bronchiseptica are closely-related pathogenic bacteria.