Assistant Professor, College of Veterinary Medicine
KEYWORDS: Pathogenesis of Vibrio Cholerae
The recent completion of many bacterial genome sequences revealed the presence of genes encoding various sodium-dependent systems in orgamisms, including some that were not known to have a primary sodium cycle of energy. Analysis of bacterial genome sequences shows that many human and animal pathogens encode primary membrane Na+ pumps and a number of Na+-dependent permeases. This indicates that these bacteria can utilize Na+ as a coupling ion instead of, or in addition to the H+ cycle. This capability to use a Na+ cycle may well be an important virulence factor for some pathogens and could provide a target for development of a novel intervention strategy. Indeed, the recent discovery of an effective natural antibiotic, korormicin, targeted against the Na+-translocating NADH:ubiquinone oxidoreductase, NQR, suggests the potential use of Na+ pumps as a drug target. Moreover, anti-microbial potential of other inhibitors of the Na+ cycle, such as monensin, Li+ and Ag+ ions, and amiloride derivatives have been previously reported. During this project we intend to construct and analyze defined mutants in Na+-extruding enzymes in V. cholerae as a first step towards a better understanding of this complex system in bacteria. The long-term goal is to identify novel drug targets amongst these enzymes and develop a potentially new class of anti-infectives to combat bacterial infections by pathogens that utilize sodium as a coupling ion. V. cholerae represents one of the best model organism for a comprehensive and detailed analysis of the sodium cycle of energy, as it has been experimentally demonstrated to utilize Na+ as a coupling ion and appears to possess a multitude of Na+-dependent systems.