Gayatri  Vedantam, Ph.D.
Assistant Professor

Members of the genus Bacteroides are obligately anaerobic human colonic bacteria, accounting for about 30 percent of normal fecal flora. However, they can also be significant opportunistic pathogens responsible for a variety of intra-abdominal infections, abscesses and peritonitis, and are an important cause of morbidity and mortality in man. Increasing antibiotic resistance in Bacteroides has been reported from around the world, and is primarily due to the exchange of mobile DNA by conjugative transfer.

Our research involves the isolation and characterization of new conjugal elements from Bacteroides spp that are involved in the acquisition and dissemination of antibiotic resistance genes. We are currently studying a mobilizable transposon Tn5520 from B. fragilis clinical isolate LV23. Tn5520 is the smallest mobilizable transposon reported to date from any bacterium (4692 base pairs). Tn5520 is transferable in B. fragilis and in E. coli and also transposes in E. coli. The ends of Tn5520 contain imperfect inverted repeats, and the transposon does not modify its target site. Tn5520 carries only two genes that encode an integrase and a mobilization (Mob) protein respectively. We have shown that the single Mob protein is sufficient to confer transfer potential on Tn5520, and to other non-transferable plasmids in cis. Thus, this Mob protein is unique, since it is multifunctional, performing all the reactions required to initiate DNA transfer.  We are currently intensively studying this Mob protein and the DNA to which it binds using electrophoretic mobility shift assays, nicking assays and localization studies.

We have also captured a large conjugative transposon (BTF37) from B. fragilis clinical isolate LV23.  BTF37 is autonomously transferable in both Bacteroides spp and E. coli, and encodes all functions required for conjugative transfer including DNA processing proteins, and mating apparatus proteins. Our investigations are currently focused on specific genes harbored by BTF37 that encode pilus-support and Type IV secretion proteins that are important for establishment for mating pairs during conjugation, and may also be involved in the formation of the mating pore. We are currently using MALDI-TOF spectroscopy, cloning, RT-PCR, Q-PCR and other molecular biology approaches to study BTF37. 

One long-term goal of these research endeavors is to identify proteins or cell-surface structures in Bacteroides spp that could be therapeutic targets for specific elimination of antibiotic-resistant organisms from normal colonic flora.

Vedantam G, Knopf S, Hecht DW.( 2006). Bacteroides fragilis mobilizable transposon Tn5520 requires a 71 base pair origin of transfer sequence and a single mobilization protein for relaxosome formation during conjugation. 
Mol Microbiol. 59(1):288-300. 

Vedantam, G.  and D.W. Hecht (2003). Antibiotics and Anaerobes.  Invited review. Curr. Op. Microbiol. 6(5); 457-461.

Vedantam, G. and D.W. Hecht. (2002). Isolation and Characterization of BTF-37: Chromosomal DNA Captured from Bacteroides fragilis that Confers Self-Transferability, and Expresses a Pilus-Like Structure in Bacteroides spp and Escherichia coli. J. Bacteriol. 184(3):728-38.

Vedantam, G., T. J. Novicki and D.W. Hecht. (1999). Bacteroides fragilis transfer factor Tn5520: The smallest bacterial mobilizable transposon containing single integrase and mobilization genes that function in E. coli. J. Bacteriol. 181(8):2564-2571.

Hecht, D.W., G. Vedantam and J.R. Osmolski.  (1999). Antimicrobial susceptibility testing in anaerobes - what now? Anaerobe 5:421-429.        

Search PubMed for a complete listing of Gayatri Vedantam's publications

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