Dr. Hung Ton-That
The University of Texas Health Science Center at Houston
Department of Microbiology & Molecular Genetics
- 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).
Program in Microbiology and Molecular Genetics