Skip to main content

Research Repository

Advanced Search

A Role for Lactate Dehydrogenases in the Survival of Neisseria gonorrhoeae in Human Polymorphonuclear Leukocytes and Cervical Epithelial Cells

Atack, John M.; Ibranovic, Ines; Ong, Cheryl-Lynn Y.; Djoko, Karrera Y.; Chen, Nathan H.; vanden Hoven, Rachel; Jennings, Michael P.; Edwards, Jennifer L.; McEwan, Alastair G.

Authors

John M. Atack

Ines Ibranovic

Cheryl-Lynn Y. Ong

Nathan H. Chen

Rachel vanden Hoven

Michael P. Jennings

Jennifer L. Edwards

Alastair G. McEwan



Abstract

Lactate is an abundant metabolite, produced by host tissues and commensal organisms, and it represents an important potential carbon source for bacterial pathogens. In the case of Neisseria spp., the importance of the lactate permease in colonization of the host has been demonstrated, but there have been few studies of lactate metabolism in pathogenic Neisseria in the postgenomic era. We describe herein the characterization of genome-annotated, respiratory, and substrate-level lactate dehydrogenases (LDHs) from the obligate human pathogen Neisseria gonorrhoeae. Biochemical assays using N. gonorrhoeae 1291 wild type and isogenic mutant strains showed that cytoplasmic LdhA (NAD+-dependent D-lactate dehydrogenase) and the membrane-bound respiratory enzymes, LdhD (D-lactate dehydrogenase) and LldD (L-lactate dehydrogenase) are correctly annotated. Mutants lacking LdhA and LdhD showed greatly reduced survival in neutrophils compared with wild type cells, highlighting the importance of D-lactate metabolism in gonococcal survival. Furthermore, an assay of host colonization using the well-established human primary cervical epithelial cell model revealed that the two respiratory enzymes make a significant contribution to colonization of and survival within the microaerobic environment of the host. Taken together, these data suggest that host-derived lactate is critical for the growth and survival of N. gonorrhoeae in human cells.

Citation

Atack, J. M., Ibranovic, I., Ong, C. Y., Djoko, K. Y., Chen, N. H., vanden Hoven, R., …McEwan, A. G. (2014). A Role for Lactate Dehydrogenases in the Survival of Neisseria gonorrhoeae in Human Polymorphonuclear Leukocytes and Cervical Epithelial Cells. The Journal of Infectious Diseases, 210(8), 1311-1318. https://doi.org/10.1093/infdis/jiu230

Journal Article Type Article
Acceptance Date Apr 4, 2014
Online Publication Date Apr 15, 2014
Publication Date 2014-10
Deposit Date Sep 6, 2017
Journal The Journal of Infectious Diseases
Print ISSN 0022-1899
Electronic ISSN 1537-6613
Publisher Oxford University Press
Peer Reviewed Peer Reviewed
Volume 210
Issue 8
Pages 1311-1318
DOI https://doi.org/10.1093/infdis/jiu230