Dr. Hung Ton-That

Regular Member

The University of Texas Health Science Center at Houston
Medical School
Department of Microbiology & Molecular Genetics

 Research Interests:

• Molecular assembly on the cell surface of Gram-positive bacteria
• Bacterial pathogenesis
• Host-pathogen interactions

Gram-positive bacteria assemble on their surface covalently linked protein polymers, known as pili or fimbriae, that enable these bacteria to adhere to specific host tissues and initiate a pathogenic program. A typical pilus contains a major pilin forming the shaft and one or more minor pilin subunits. The heteromeric pilus is assembled by a specific transpeptidase enzyme called sortase. While the joining of individual pilins into a polymer is catalyzed by a pilus-specific sortase, anchoring of the pilus to the cell wall peptidoglycan is carried out by the housekeeping sortase. We use Actinomyces naeslundi, Corynebacterium diphtheriae and Streptococcus agalactiae (group B Streptococcus, GBS) as experimental models to answer three fundamental problems: (1) the mechanism of pilus assembly in Gram-positive bacteria, (2) the universality of the proposed mechanism, and (3) the role of pili in bacterial pathogenesis.

Some of outstanding questions are:

•            What governs the decision between pilus polymerization and cell wall anchoring?
•            What determines the substrate specificity of a sortase?
•            How does the housekeeping sortase modulate pilus assembly?
•            Is pilus expression and assembly regulated by host cues during infection?
•            What roles do pili play during in vivo infection?
•            How do pilins trigger inflammatory responses?

Our multidisciplinary approaches to these studies is a combination of immuno-fluorescence and electron microscopy, mass spectrometry, biochemical assays, molecular biology, immunology and in vitro and in vivo infection models (tissue cultures and rodent models).

Publications

Program Affiliation:

Program in Microbiology and Molecular Genetics