The L-lactate dehydrogenase LldD contributes to oxidative stress resistance, survival from neutrophils, and host colonization in Neisseria gonorrhoeae

Jerri M Lankford; Willis E Barr; Cole A Andersen; Amitha A Karuppiah; Keena S Thomas; Ian J Glomski; Alison K Criss; Aimee D Potter

doi:10.1101/2025.11.17.688940

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The L-lactate dehydrogenase LldD contributes to oxidative stress resistance, survival from neutrophils, and host colonization in Neisseria gonorrhoeae

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The L-lactate dehydrogenase LldD contributes to oxidative stress resistance, survival from neutrophils, and host colonization in Neisseria gonorrhoeae

Jerri M Lankford, Willis E Barr, Cole A Andersen, Amitha A Karuppiah, Keena S Thomas, Ian J Glomski, Alison K Criss and Aimee D Potter

bioRxiv

Cold Spring Harbor Laboratory

11/17/2025

DOI: 10.1101/2025.11.17.688940

PMCID: PMC12667838

PMID: 41332523

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https://doi.org/10.1101/2025.11.17.688940View

Preprint (Author's original)This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

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 (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, but not LutACB, 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 Iowa
Willis E Barr
Cole A Andersen
Amitha A Karuppiah - University of Iowa
Keena S Thomas - University of Virginia
Ian J Glomski - University of Virginia
Alison K Criss - University of Virginia
Aimee D Potter - University of Iowa
Resource Type: Preprint
Publication Details: bioRxiv
DOI: 10.1101/2025.11.17.688940
PMID: 41332523
PMCID: PMC12667838
eISSN: 2692-8205
Publisher: Cold Spring Harbor Laboratory; United States
Language: English
Date posted: 11/17/2025
Academic Unit: Microbiology and Immunology
Record Identifier: 9985090729902771

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