title: A role for lactate dehydrogenases in the survival of Neisseria gonorrhoeae in human polymorphonuclear leukocytes and cervical epithelial cells.
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.
authors.affiliation: School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane Institute for Glycomics, Griffith University, Gold Coast Campus, Gold Coast, Queensland, Australia.
authors.forename: John M
authors.initials: JM
authors.lastname: Atack
authors.affiliation: School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane.
authors.forename: Ines
authors.initials: I
authors.lastname: Ibranovic
authors.affiliation: School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane.
authors.forename: Cheryl-Lynn Y
authors.initials: CL
authors.lastname: Ong
authors.affiliation: School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane.
authors.forename: Karrera Y
authors.initials: KY
authors.lastname: Djoko
authors.affiliation: School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane.
authors.forename: Nathan H
authors.initials: NH
authors.lastname: Chen
authors.affiliation: School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane.
authors.forename: Rachel
authors.initials: R
authors.lastname: Vanden Hoven
authors.affiliation: School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane Institute for Glycomics, Griffith University, Gold Coast Campus, Gold Coast, Queensland, Australia.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Jennings
authors.affiliation: Center for Microbial Pathogenesis, The Research Institute at Nationwide Children's Hospital, Columbus, Ohio.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Edwards
authors.affiliation: School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane.
authors.forename: Alastair G
authors.initials: AG
authors.lastname: McEwan
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002584:Cervix Uteri / Q000166:cytology*; D004269:DNA, Bacterial / Q000235:genetics; D004847:Epithelial Cells / Q000382:microbiology*; D005260:Female; D015964:Gene Expression Regulation, Bacterial; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D045022:Lactate Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009344:Neisseria gonorrhoeae / Q000201:enzymology*; D009504:Neutrophils / Q000382:microbiology*
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D045022:Lactate Dehydrogenases
keywords: cervical epithelial cells; gonococcus; intracellular metabolism; lactate; neutrophil; respiration
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