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, biofilm formation and bacterial pathogenesis

Gram-positive pathogens 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 tandem transpeptidase enzymes called sortases. A pilus-specific sortase catalyzes the extension of pilus heteropolymers. The product of this cyclic polymerization is handed directly to the housekeeping sortase, which completes the assembly process by anchoring the resulting pilus polymer to the bacterial peptidoglycan. Many aspects of this biphasic pilus assembly are not well understood. Using Actinomyces naeslundii, Corynebacterium diphtheriae and Streptococcus agalactiae (group B Streptococcus, GBS) as experimental models, we aim to address the following fundamental problems in pilus assembly and pilus-mediated bacterial pathogenesis:
•              What governs the decision between pilus polymerization and cell wall anchoring?
•              What determines the substrate specificity of a sortase?
•              How the housekeeping sortase modulates pilus assembly?
•              How pilus assembly is regulated by host cues during infection?
•              How pili mediate biofilm formation and bacterial pathogenesis?

Lab Rotations: Available

The projects will be designed centering on the these major problems above and individual student interests. Our multidisciplinary approach to these studies is a combination of electron microscopy, biochemistry, structural biology, biophysics, genetics, immunology, and pathogenesis (tissue cultures and rodent models).

Selected Publications:
  • Reardon-Robinson, M.E., Wu, C., Mishra, A., Chang, C., Bier, N., Das, A., Ton-That, H. (2014). Pilus hijacking by a bacterial coaggregation factor critical for oral biofilm development. Proc Natl Acad Sci U S A. (In Press).
  • Kang, H.J., Paterson, N.G., Kim, C.U., Middleditch, M., Chang, C., Ton-That, H., Baker, E.N. (2014). A slow-forming isopeptide bond in the structure of the major pilin SpaD from Corynebacterium diphtheriae has implications for pilus assembly. Acta Crystallogr D Biol Crystallogr. (In Press)
  • Broadway, M.M., Rogers, E.A., Chang, C., Huang, I.H., Dwivedi, P., Yildirim, S., Schmitt, M.P., Das, A., Ton-That, H. (2013) Pilus gene pool variation and the virulence of Corynebacterium diphtheriae clinical isolates during infection of a nematode. Journal of Bacteriology. 195:3774-3783. [abstract].
  • Sillanpää, J., Chang, C., Singh, K.V., Montealegre, M.C., Nallapareddy, S.R., Harvey, B.R., Ton-That, H., Murray, B.E. (2013). Contribution of individual Ebp pilus subunits of Enterococcus faecalis OG1RF to pilus biogenesis, biofilm formation and urinary tract infection. Plos One. 8(7):e68813. [abstract].
  • Krishnan, V., Dwivedi, P., Kim, B.J., Samal, A., Macon, K., Ma, X., Mishra, A., Doran, K.S., Ton-That, H. Narayana, S.V.L. (2013) Structure of Streptococcus agalactiae tip pilin GBS104: a model for GBS pili assembly and host interactions. Acta Crystallogr D Biol Crystallogr, 69:1073–1089. [abstract]
  • Chang, C., Huang, I-H., Hendrickx, A.P., Ton-That, H. (2013). Visualization of Gram-positive bacterial pili. Methods Mol Biol., 966:77-95. [abstract]
  • Trost, E., Blom, J., de Castro Soares, S., Huang, I-H., Al-Dilaimi, A., Schroeder, J., Jaenicke, S., Dorella, F., Rocha, F., Miyoshi, A., Azevedo, V., Schneider, M., Silva, A., Camello, T., Sabbadini, P., Santos, C., Santos, L., Hirata, R., Mattos-Guaraldi, A., Efstratiou, A., Schmitt, M., Ton-That, H., Tauch, A. (2012) Pangenomics of Corynebacterium diphtheriae: Insights into the genomic diversity of pathogenic isolates from cases of classical diphtheria, endocarditis and pneumonia. Journal of Bacteriology, 194(12):3199-215 [abstract]
  • Wu, C., Mishra, A., Reardon, M.E., Huang, I-H., Counts, S.C., Das, A., Ton-That, H. (2012) Structural determinants of Actinomyces sortase SrtC2 required for membrane localization and assembly of type 2 fimbriae for interbacterial coaggregation and oral biofilm formation. Journal of Bacteriology, 194(10):2561-2539. [abstract]
  • Khare, B., Fu, Z.Q., Huang, I-H., Ton-That, H., Narayana, S.V. (2011) The crystal structure analysis of group B Streptococcus sortase C1: a model for the "lid" movement upon substrate binding. Journal of Molecular Biology, 414(4):563-77. [abstract]
  • Khare, B., Krishnan, V., Rajashankar, K., Huang, I-H., Ma, X., Ton-That, H., Narayana, S.V. (2011). Structural differences between the Streptococcus agalactiae housekeeping and pilus-specific sortases SrtA and SrtC1. PloS One, 6(8):e22995.[abstract]
  • Mishra, A., Devarajan, B., Reardon, M.E., Dwivedi, P., Krishnan, V., Cisar, J.O., Das, A., Narayana, S.V.,Ton-That, H. (2011). Two autonomous structural modules in the fimbrial shaft adhesin FimA mediate actinomyces interactions with Streptococci and host cells during oral biofilm development. Molecular Microbiology, 81(5):1205–1220. [abstract]
  • Rogers, E.A., Das, A., Ton-That, H. (2011). Adhesion by pathogenic Corynebacteria. Advances in Experimental Medicine and Biology. 715:91-103. [abstract]
  • Wu, C., Mishra, A., Yang, J., Cisar, J.O., Das, A., Ton-That, H. (2011). Dual function of a tip fimbrillin of Actinomyces in fimbrial assembly and receptor binding. Journal of Bacteriology, 193(13):3197-206. [abstract]
  • Vengadesan, K., Ma, X., Dwivedi, P., Ton-That, H., Narayana, S.V. (2011). A model for Group B Streptococcus pilus type 1: The structure of a 35-kDa C-terminal fragment of the major pilin GBS80. Journal of Molecular Biology, 407(5):731-43. [abstract]
  • Chang, C., Mandlik, A., Das, A., Ton-That, H. (2011). Cell surface display of minor pilin adhesins in the form of a simple heterodimeric assembly in Corynebacterium diphtheriae. Molecular Microbiology, 79(5):1236-47. [abstract]
  • [Search PubMed for more papers by Hung Ton-That]