Department of Molecular Bacteriology

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 can 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 these toxins. These approaches together will help to clarify the structure and function of these bacterial toxins.

(2) Analysis of whooping cough pathogenesis.
Bordetella pertussis, a pathogenic bacteria, infects the human respiratory tract and causes whooping cough, which is characterized by paroxysmal coughing. There are two signficant questions about the pathogenesis of B.pertussis infection. First, why does B. pertussis infect humans but no other mammals? Second, how does this bacterium induce the paroxysmal coughing? We are currently examining the pathology of the disease and the function of B. pertussis 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 toxic effects by modifying important functions of the host cells. Signficantly, the relevant physiological functions of the cells can also be determined by dissecting the actions of the bacterial toxins.

Fig. 2: Overall structure of the intracellular active region of Pasteurella multocida toxin, which is composed of three domains and has a Trojan horse-like shape.

Fig. 3: Bordetella pertussis, B. parapertussis, and B. bronchiseptica are closely-related pathogenic bacteria. B. bronchiseptica has the largest genome and the broadest host range, whereas B. pertussis has the smallest genome and the narrowest host range. It is believed that B. pertussis evolved from a B. bronchiseptica lineage through the deletion and/or translocation of a large number of genes.