Hung Ton-That, Ph.D.
- Associate Professor
Department of Microbiology &
University of Texas-Houston Medical School
6431 Fannin Street, MSE R224
Houston, Texas 77030
Telephone: (713) 500-5468
Laboratory telephone: (713) 500-5462
Ph.D., University of California, Los Angeles, 2000
Postdoctoral Fellow, University of Chicago
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 approach 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).
Postdoctoral Position: Available
A postdoctoral research position is available to study molecular assembly and function of gram-positive bacterial pili/fimbriae. Applicants should have a Ph.D. in microbiology, molecular biology, biochemistry or a closely related field. Expertise in host-pathogen interaction and bacterial pathogenesis is desirable. Candidates with immunology background are encouraged to apply. Please email a brief description of research interests, a detailed CV, and three letters of reference to Dr. Hung Ton-That.
- Trost E, Blom J, de Castro Soares S, Huang IH, 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 and 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 ME, Huang I-H, Counts SC, Das A and 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 ZQ, Huang IH, Ton-That H and Narayana SV (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 IH, Ma X, Ton-That H, and Narayana SV (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 ME, Dwivedi P, Krishnan V, Cisar JO, Das A, Narayana SV and 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 EA, Das A and 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 JO, Das A and 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 SV (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]
- Mishra A, Wu C, Yang J, Cisar JO, Das A, Ton-That H. (2010) The Actinomyces oris type 2 fimbrial shaft FimA mediates co-aggregation with oral streptococci, adherence to red blood cells and biofilm development. Molecular Microbiology, 77(4), 841–854. [abstract]
- Wu C, Ton-That H. (2010) Allelic exchange in Actinomyces oris with mCherry fluorescence counterselection. Appl Environ Microbiol, 76(17):5987-9. [abstract]
- Sillanpää J, Nallapareddy SR, Singh KV, Prakash VP, Fothergill T, Ton-That H, Murray BE. (2010) Characterization of the ebp pilus-encoding operon of Enterococcus faecium and its role in biofilm formation and virulence in a murine model of urinary tract infection. Virulence, 1(4):236-246. [abstract]
- Khare B, Samal A, Vengadesan K, Rajashankar KR, Ma X, Huang IH, Ton-That H, Narayana SV. (2010) Preliminary crystallographic study of the Streptococcus agalactiae sortases, sortase A and sortase C1. Acta Crystallogr Sect F Struct Biol Cryst Commun. 66(Pt 9):1096-100. [abstract]
- Vengadesan K, Ma X, Dwivedi P, Ton-That H, Narayana SV. (2010) Purification, crystallization and halide phasing of a Streptococcus agalactiae backbone pilin GBS80 fragment. Acta Crystallogr Sect F Struct Biol Cryst Commun. 66(Pt 12):1666-9. [abstract]
- Kang HJ, Paterson NG, Gaspar AH, Ton-That H* and Baker EN*. (2009) The Corynebacterium diphtheriae shaft pilin SpaA is built of tandem Ig-like modules with stabilizing isopeptide and disulfide bonds. PNAS, 106(40):16967-71. [abstract]
- Guttilla IK, Gaspar AH, Swierczynski A, SwaminathanA, Dwivedi P, Das A, Ton-That H. (2009) Acyl enzyme intermediates in the sortase-catalyzed pilus morphogenesis in Gram-positive bacteria. Journal of Bacteriology, 191(18):5603-12. [abstract]
- A Mandlik, A Das and Ton-That H. (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 Ton-That H. (2008) Pili in Gram-positive bacteria: assembly, involvement in colonization and biofilm development. Trends in Microbiology, 16(1):33-40. [abstract]
- [Search PubMed for more papers by Hung Ton-That]
Location & Contact
6431 Fannin Street,
Houston, Texas 77030
P.O. Box 20708
Houston, Texas 77225
Our affiliates include the following:
- Departmental Faculty
- Theresa M. Koehler, Ph.D.
- Peter J. Christie, Ph.D.
- Nicholas De Lay, Ph.D.
- Jesus Eraso, Ph.D.
- Danielle Garsin, Ph.D.
- Heidi Kaplan, Ph.D.
- Samuel Kaplan, Ph.D.
- Nayun Kim, Ph.D.
- Ziyin Li, Ph.D.
- Jiqiang (Lanny) Ling, Ph.D.
- Michael C. Lorenz, Ph.D.
- Chris Mackenzie, Ph.D.
- William Margolin, Ph.D.
- Kevin A. Morano, Ph.D.
- Hung Ton-That, Ph.D.
- Ambro van Hoof, Ph.D.
- Departmental Faculty - Cross Appointees
- William Dowhan, Ph.D.
- Millicent Goldschmidt, Ph.D.
- Barrett Harvey, Ph.D.
- Jun Liu, Ph.D.
- Barbara E. Murray, M.D.
- Steven J. Norris, Ph.D.
- John L. Spudich, Ph.D.
- Adjunct Faculty
- Magnus Höök, Ph.D.
- Gregory S. May, Ph.D.
- Yi Xu, Ph.D.