Searching for New Antimicrobial Targets: Na+ Cycle in Energetics of Bacterial Pathogens
Outbreaks of microbial infections (tuberculosis, cholera, etc.) endangering lives of civilians and military personnel alike are inevitable consequences of social and military crises. The situation is further exacerbated by the current global crisis of antimicrobial therapy caused by common misuse of broad-range antibiotics and the resulting proliferation of drug-resistant strains. Despite the resurrected interest in alternative approaches, such as the development of adjunctive immunotherapy, search for new targets for prospective antimicrobials apparently remains the most viable option in the management of microbial infections. A consensus is emerging that a new generation of antimicrobial remedies should include precisely targeted, ideally – pathogen-specific drugs. As it is evident from cross-genome comparisons, Na+ pumping systems of different types (comprising a “sodium cycle” in bacterial membrane energetics) are “overrepresented” in microbial pathogens. This might be due to a peculiar evolutionary relationship between the “mainstream” type of bacterial energetics based on the transmembrane circulation of proton (H+ cycle) and more archaic Na+ cycle. Wide spreading of elements of Na+ cycle among different pathogens makes these systems attractive targets for prospective development of novel, narrowly targeted antimicrobials. In this communication, a “target potential” of the primary respiratory Na+ pump, NQR, and secondary Na+ pumps, NhaA/B, is discussed.
KeywordsPorphyromonas Gingivalis Yersinia Pestis Buruli Ulcer Ubiquinone Oxidoreductase Obligate Intracellular Parasite
Many thanks are due to Dr. Deborah Court (University of Manitoba) for critical reading of the manuscript. Work in the author’s lab is currently supported by the Natural Sciences and Engineering Research Council of Canada (operating grant No. 227414-09).
- 42.Bogachev AV, Verkhovsky MI (2005) Na+-translocating NADH:quinone oxidoreductase: progress achieved and prospects of investigations. Biochemistry (Moscow) 70:177–185Google Scholar
- 61.Shalitin Y, Segal D. Gur D (2002) 2-Aminoperimidine is an effector of cholinesterases. In: Proceedings of the XIth international symposium on cholinergic mechanisms-function and dysfunction, St. Moritz, 5–9 May 2002Google Scholar