Dr. Wu's isolation and characterization of the Fap1 molecule, a glycosylated fimbrial structural subunit of Streptococcus parasanguis, was a significant breakthrough in understanding the basic for fimbrial biosynthesis and adhesion in Gram-positive bacteria. Fap1-like molecules and genes involved in Fapl glycosylation are not only highly conserved across oral streptococci but are also present in Streptococcus pneumoniae and in the staophlococci. Dr. Wu's current research on the glycoslylation of Fap1 is extremely exciting. It is likely that a universal glycosylation machinery is present in Gram-positive bacteria and the findings from these studies would be applicable to other organisms. Recently, he identified a gene cluster that is required for the glycosylation of Fap1. He is currently in the process of determining the biosynthetic pathway by which Fap1 is glycosylated using molecular genetic, structural biology, and biochemical approaches. With the support of a K22 award, Dr. Wu will take formal courses in mass spectrometry and bioinformatics and receive hands-on training in Mass spectrometry analysis of the carbohydrate structure and biochemical analysis of key enzymes involved in protein glycosylation. The support of a K22 will provide Dr. Wu with new skills and knowledge in carbohydrate biochemistry that will position him to pursue new avenues in the study of glycosylation of streptococcql adhesions. Dr. Wu is in a unique position to determine the mechanisms of prokaryotic glycosylation and Gram-positive fimbrial biogenesis as the explict genetic tools have been generated in Dr. Fives-Taylor's laboratory over the last 20 years. Dr. Wu's strength in molecular genetics coupled with the training in carbohydrate biochemistry specifically in mass spectrometry analysis and enzymology will enhance his career development in this exciting research area. The results of this proposal will help define the biosynthetic pathway for Fap1 glycosylation. New genes in the pathway may endow microbes with new effector functions or aid in the evasion of host defense, strategies that are important components of disease-causing capabilities of a number of bacterial pathogens. Therefore, elucidation of Fap1 glycosylation may provide a framework for understanding the role of glycoslyation in bacterial pathogenesis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Career Transition Award (K22)
Project #
5K22DE014726-05
Application #
7229442
Study Section
NIDCR Special Grants Review Committee (DSR)
Program Officer
Hardwick, Kevin S
Project Start
2003-06-04
Project End
2008-05-31
Budget Start
2007-06-01
Budget End
2008-05-31
Support Year
5
Fiscal Year
2007
Total Cost
$135,000
Indirect Cost
Name
University of Alabama Birmingham
Department
Dentistry
Type
Schools of Dentistry
DUNS #
063690705
City
Birmingham
State
AL
Country
United States
Zip Code
35294
Zhou, Meixian; Wu, Hui (2009) Glycosylation and biogenesis of a family of serine-rich bacterial adhesins. Microbiology 155:317-27
Li, Yirong; Chen, Yabing; Huang, Xiang et al. (2008) A conserved domain of previously unknown function in Gap1 mediates protein-protein interaction and is required for biogenesis of a serine-rich streptococcal adhesin. Mol Microbiol 70:1094-104
Peng, Zhixiang; Fives-Taylor, Paula; Ruiz, Teresa et al. (2008) Identification of critical residues in Gap3 of Streptococcus parasanguinis involved in Fap1 glycosylation, fimbrial formation and in vitro adhesion. BMC Microbiol 8:52
Bu, Su; Li, Yirong; Zhou, Meixian et al. (2008) Interaction between two putative glycosyltransferases is required for glycosylation of a serine-rich streptococcal adhesin. J Bacteriol 190:1256-66
Peng, Z; Wu, H; Ruiz, T et al. (2008) Role of gap3 in Fap1 glycosylation, stability, in vitro adhesion, and fimbrial and biofilm formation of Streptococcus parasanguinis. Oral Microbiol Immunol 23:70-8
Zhou, Meixian; Peng, Zhixiang; Fives-Taylor, Paula et al. (2008) A conserved C-terminal 13-amino-acid motif of Gap1 is required for Gap1 function and necessary for the biogenesis of a serine-rich glycoprotein of Streptococcus parasanguinis. Infect Immun 76:5624-31
Zhou, Meixian; Fives-Taylor, Paula; Wu, Hui (2008) The utility of affinity-tags for detection of a streptococcal protein from a variety of streptococcal species. J Microbiol Methods 72:249-56
Chen, Qiang; Sun, Baiming; Wu, Hui et al. (2007) Differential roles of individual domains in selection of secretion route of a Streptococcus parasanguinis serine-rich adhesin, Fap1. J Bacteriol 189:7610-7
Wu, Hui; Zeng, Meiqin; Fives-Taylor, Paula (2007) The glycan moieties and the N-terminal polypeptide backbone of a fimbria-associated adhesin, Fap1, play distinct roles in the biofilm development of Streptococcus parasanguinis. Infect Immun 75:2181-8
Wu, Hui; Bu, Su; Newell, Peter et al. (2007) Two gene determinants are differentially involved in the biogenesis of Fap1 precursors in Streptococcus parasanguis. J Bacteriol 189:1390-8

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