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, 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. Examples 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?
We use Actinomyces naeslundii, Corynebacterium diphtheriaeand Streptococcus agalactiae(group B Streptococcus, GBS) as experimental models to answer these fundamental problems and investigate the role of pili in biofilm formation and bacterial infection.
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).
- Broadway MM, Rogers EA, Chang C, Huang IH, Dwivedi P, Yildirim S, Schmitt MP, Das A, and Ton-That H. (2013) Pilus gene pool variation and the virulence of Corynebacterium diphtheriae clinical isolates during infection of a nematode. Journal of Bacteriology (In Press).
- Sillanpää J, Chang C, Singh KV, Montealegre MC, Nallapareddy SR, Harvey BR, Ton-That H and Murray BE (2013). Contribution of Individual Ebp Pilus Subunits of Enterococcus faecalis OG1RF to Pilus Biogenesis, Biofilm Formation and Urinary Tract Infection. Plos One, (In Press)
- Krishnan V, Dwivedi P, Kim BJ, Samal A, Macon K, Ma X, Mishra A, Doran KS, Ton-That H and Narayana SVL. (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 IH, Hendrickx AP, and 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 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.