Dr. Hung Ton-That
The University of Texas Health Science Center at Houston
Department of Microbiology & Molecular Genetics
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 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
Title: Associate Professor
Ph.D. - University of California at Los Angeles - 2000