Journal article
The L-lactate dehydrogenase LldD contributes to oxidative stress resistance, survival from neutrophils, and host colonization in Neisseria gonorrhoeae
Infection and immunity, PMID 246127
01/30/2026
DOI: 10.1128/iai.00644-25
PMCID: PMC12974116
PMID: 41616255
Abstract
Metabolic adaptation to the host environment is a key determinant of bacterial pathogenesis, enabling both colonization and invasive disease. This is particularly true for
(Gc), the causative agent of gonorrhea, which lacks effector-injecting secretion systems or toxins. Gc infection triggers a rapid influx of neutrophils (polymorphonuclear cells [PMNs) that typically kill bacteria through multiple mechanisms, including a potent oxidative burst. Despite this, Gc exhibits remarkable resistance to reactive oxygen species and readily replicates in the presence of PMNs, which is in part due to the consumption of PMN-derived lactate. Previous studies demonstrated that the lactate permease, LctP, is required for oxidative stress resistance in Gc and host colonization in a murine model of gonorrhea, suggesting that lactate utilization contributes to virulence. Gc encodes four lactate dehydrogenases (LDHs) with distinct regulation and mechanisms, including two L-LDHs, LldD and LutACB. Although either enzyme alone supports L-lactate utilization, we found that both are required for full fitness during co-colonization with PMNs, indicating some non-redundant roles. Furthermore, LldD enhances oxidative stress resistance and is required for Gc colonization in a murine model of gonorrhea, whereas LutACB is dispensable. These findings identify LldD as a key factor promoting oxidative stress resistance, survival during PMN challenge, and host colonization.
Details
- Title: Subtitle
- The L-lactate dehydrogenase LldD contributes to oxidative stress resistance, survival from neutrophils, and host colonization in Neisseria gonorrhoeae
- Creators
- Jerri M Lankford - University of IowaWillis E Barr - University of IowaCole A Andersen - University of IowaAmitha A Karuppiah - University of IowaKeena S Thomas - University of VirginiaIan J Glomski - University of VirginiaWen-Chi Huang - University of IowaAlison K Criss - University of VirginiaAimee D Potter - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Infection and immunity, PMID 246127
- DOI
- 10.1128/iai.00644-25
- PMID
- 41616255
- PMCID
- PMC12974116
- NLM abbreviation
- Infect Immun
- ISSN
- 0019-9567
- eISSN
- 1098-5522
- Publisher
- American Society for Microbiology
- Grant note
- School of Medicine, University of Virginia: Harrison Distinguished Teaching Professorship National Institutes of Health: R01AI097312, R01AI127793, R21AI161302 Roy J. and Lucille A. Carver College of Medicine, University of Iowa: Start up funds
This work was supported in part by NIH T32AI007496, NIH R01AI127793-07W2, and startup funds from the University of Iowa Carver College of Medicine to A.D.P. A.K.C. was supported by NIH R01AI097312, NIH R01AI127793, R21AI161302, and the Harrison Distinguished Teaching Professorship.
- Language
- English
- Electronic publication date
- 01/30/2026
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9985132202802771
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