The University of Texas Medical School at Houston
Department of Microbiology and Molecular Genetics

Hung Ton-That, Ph.D.

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  • Hung Ton-That, Ph.D.Associate Professor
  • Department of Microbiology &
    Molecular Genetics
  • University of Texas-Houston Medical School
    6431 Fannin Street, MSE R224
    Houston, Texas 77030
  • Telephone: (713) 500-5468
    Laboratory telephone: (713) 500-5462
    e-mail:ton-that.hung@uth.tmc.edu

Education:

Ph.D., University of California, Los Angeles, 2000

Postdoctoral Fellow, University of Chicago

Research Interests:

Pilus assembly of Gram-positive pathogens, host-pathogen interactions and bacterial pathogenesis

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?

Lab Rotations: Available

The projects will be designed centering on the three major problems above and individual student interests. 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, Caenorhabditis elegans and rodent models).

Selected Publications:
  • HJ Kang, NG Paterson, AH Gaspar, H Ton-That* and EN Baker*. (2009) The Corynebacterium diphtheriae shaft pilin SpaA is built of tandem Ig-like modules with stabilizing isopeptide and disulfide bonds. PNAS (In press).
  • IK Guttilla, AH Gaspar, A Swierczynski, A Swaminathan, P Dwivedi, A Das, H Ton-That. (2009) Acyl enzyme intermediates in the sortase-catalyzed pilus morphogenesis in Gram-positive bacteria. Journal of Bacteriology [abstract]
  • A Mandlik, A Das and H Ton-That. (2008) The molecular switch that activates the cell wall anchoring step of pilus assembly in gram-positive bacteria. PNAS, 105(37):14147-14152. [abstract]
  • A Mandlik, A Swierczynski, A Das and H Ton-That. (2008) Pili in Gram-positive bacteria: assembly, involvement in colonization and biofilm development. Trends in Microbiology, 16(1):33-40. [abstract]
  • A Swaminathan, A Mandlik, A Swierczynski, A Gaspar, A Das and H Ton-That. (2007) Housekeeping sortase facilitates the cell wall anchoring of pilus polymers in Corynebacterium diphtheriae. Molecular Microbiology, 66(4): 961–974 [abstract]
  • V Krishnan, A H Gaspar, N Ye, A Mandlik, H Ton-That, and S V L Narayana. (2007) An IgG-like domain in the minor pilin GBS52 of Streptococcus agalactiae mediates lung epithelial cell adhesion. Structure, 15(8):893–903. [abstract]
  • A Mandlik, A Swierczynski, A Das and H Ton-That. (2007) Corynebacterium diphtheriae employs specific minor pilins to target human pharyngeal epithelial cells. Molecular Microbiology, 64(1):111-124. [abstract]
  • A Mishra, A Das, J O Cisar and H Ton-That. (2007) Sortase-catalyzed assembly of distinct heteromeric fimbriae in Actinomyces naeslundii. Journal of Bacteriology, 189(8):3156-3165. [abstract]
  • A Swierczynski and H Ton-That. (2006) Type III pilus of corynebacteria: Pilus length is determined by the level of its major pilin subunit. Journal of Bacteriology, 188(17):6318-6325. [abstract]
  • A H Gaspar and H Ton-That. (2006) Assembly of distinct pilus structures on the surface of Corynebacterium diphtheriae. Journal of Bacteriology, 188(4):1526-1533. [abstract]
  • A H Gaspar, L A Maraffini, E M Glass, K L Debord, H Ton-That, and O Schneewind. (2005) Bacillus anthracis sortase A (SrtA) anchors LPXTG motif-containing surface proteins to the cell wall envelope. Journal of Bacteriology, 187(13):4646-4655. [abstract]
[Search PubMed for more papers by Hung Ton-That]