Sodium ion cycle in bacterial pathogens: Evidence from cross-genome comparisons

Analysis of the bacterial genome sequences shows that many human and animal pathogens encode primary membrane Na+ pumps, Na+-transporting dicarboxylat e decarboxylases or Na+-translocating NADH:ubiquinone oxidoreductase, 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. Th is capability to use a Na+ cycle might be an important virulence factor for such pathogens as Vibrio, cholerae, Neisseria meningitidis, Salmonella ent erica serovar Typhi, and Yersinia pestis. In Treponema pallidum, Chlamydia trachomatis, and Chlamydia pneumoniae, the Na+ gradient may well be the onl y energy source for secondary transport. A survey of preliminary genome seq uences of Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, a nd Treponema denticola indicates that these oral pathogens also rely on the Na+ cycle for at least part of their energy metabolism. The possible roles of the Na+ cycling in the energy metabolism and pathogenicity of these org anisms are reviewed. The recent discovery of an effective natural antibioti c, korormicin, targeted against the Na+-translocating NADH:ubiquinone oxido reductase, suggests a potential use of Na+ pumps as drug targets and/or vac cine candidates. The antimicrobial potential of other inhibitors of the Na cycle, such as monensin, Li+ and Ag+ ions, and amiloride derivatives, is di scussed.