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. and McEwan, Alastair G. (2014) A role for lactate dehydrogenases in the survival of Neisseria gonorrhoeae in human polymorphonuclear leukocytes and cervical epithelial cells. Journal of Infectious Diseases, 210 8: 1311-1318. doi:10.1093/infdis/jiu230


Author 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.
Title A role for lactate dehydrogenases in the survival of Neisseria gonorrhoeae in human polymorphonuclear leukocytes and cervical epithelial cells
Formatted title
A role for lactate dehydrogenases in the survival of Neisseria gonorrhoeae in human polymorphonuclear leukocytes and cervical epithelial cells
Journal name Journal of Infectious Diseases   Check publisher's open access policy
ISSN 0022-1899
1537-6613
Publication date 2014-04-15
Year available 2014
Sub-type Article (original research)
DOI 10.1093/infdis/jiu230
Open Access Status
Volume 210
Issue 8
Start page 1311
End page 1318
Total pages 28
Place of publication Cary, NC, United States
Publisher Oxford University Press
Collection year 2015
Language eng
Formatted 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 colonisation of the host has been demonstrated, but there have been few studies of lactate metabolism in pathogenic Neisseria in the post-genomic era. We describe herein the characterisation of genome-annotated, respiratory and substrate-level lactate dehydrogenases 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 when compared to wild-type cells, highlighting the importance of D-lactate metabolism in gonococcal survival. Further, an assay of host colonisation using the well-established human primary cervical epithelial cell model revealed that the two respiratory enzymes make a significant contribution to colonisation 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.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online ahead of print 15 April 2014.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Chemistry and Molecular Biosciences
 
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Created: Mon, 05 May 2014, 15:19:55 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences