Energetics of Pathogenic Bacteria and Opportunities for Drug Development

Gregory M. Cook, Chris Greening, Kiel Hards, Michael Berney

Research output: Chapter in Book/Report/Conference proceedingChapter (Book)Researchpeer-review

59 Citations (Scopus)

Abstract

The emergence and spread of drug-resistant pathogens and our inability to develop new antimicrobials to overcome resistance has inspired scientists to consider new targets for drug development. Cellular bioenergetics is an area showing promise for the development of new antimicrobials, particularly in the discovery of new anti-tuberculosis drugs where several new compounds have entered clinical trials. In this review, we have examined the bioenergetics of various bacterial pathogens, highlighting the versatility of electron donor and acceptor utilisation and the modularity of electron transport chain components in bacteria. In addition to re-examining classical concepts, we explore new literature that reveals the intricacies of pathogen energetics, for example, how Salmonella enterica and Campylobacter jejuni exploit host and microbiota to derive powerful electron donors and sinks; the strategies Mycobacterium tuberculosis and Pseudomonas aeruginosa use to persist in lung tissues; and the importance of sodium energetics and electron bifurcation in the chemiosmotic anaerobe Fusobacterium nucleatum. A combination of physiological, biochemical, and pharmacological data suggests that, in addition to the clinically-approved target F1Fo-ATP synthase, NADH dehydrogenase type II, succinate dehydrogenase, hydrogenase, cytochrome bd oxidase, and menaquinone biosynthesis pathways are particularly promising next-generation drug targets. The realisation of cellular energetics as a rich target space for the development of new antimicrobials will be dependent upon gaining increased understanding of the energetic processes utilised by pathogens in host environments and the ability to design bacterial-specific inhibitors of these processes.

Original languageEnglish
Title of host publicationAdvances in Microbial Physiology
Subtitle of host publicationAdvances in Bacterial Pathogen Biology
EditorsRobert K Poole
Place of PublicationSan Diego CA USA
PublisherAcademic Press
Pages1-62
Number of pages62
Volume65
Edition1
ISBN (Print)9780128001424
DOIs
Publication statusPublished - 1 Jan 2014
Externally publishedYes

Publication series

NameAdvances in Microbial Physiology
Volume65
ISSN (Print)0065-2911

Keywords

  • Bacterial energetics
  • Drug targets
  • Pathogenic bacteria
  • Physiology
  • Respiration

Cite this

Cook, G. M., Greening, C., Hards, K., & Berney, M. (2014). Energetics of Pathogenic Bacteria and Opportunities for Drug Development. In R. K. Poole (Ed.), Advances in Microbial Physiology: Advances in Bacterial Pathogen Biology (1 ed., Vol. 65, pp. 1-62). (Advances in Microbial Physiology; Vol. 65). Academic Press. https://doi.org/10.1016/bs.ampbs.2014.08.001