# Neisseria gonorrhoeae central metabolism in the context of neutrophilic inflammation

> **NIH NIH R21** · UNIVERSITY OF VIRGINIA · 2022 · $201,875

## Abstract

ABSTRACT
Neisseria gonorrhoeae (Gc) is the causative agent of the sexually transmitted disease gonorrhea. Gc is a
prominent threat to human health due to emergence of “superbug” strains that are resistant to all current
antibiotics and its clinical sequelae, including infertility and chronic pelvic pain, that have severe and lifelong
effects. Gc is highly adapted to colonize human mucosal surfaces, where it survives despite initiating a robust
inflammatory response and influx of polymorphonuclear leukocytes (PMNs or neutrophils) that typically clear
bacteria. We recently used the unbiased, genome-wide approaches of transposon-sequencing and dual RNA-
sequencing of Gc and PMNs to identify a cohort of genes contributing to successful Gc infection of PMNs. Gc
metabolic genes were overrepresented in this cohort, suggesting that Gc utilizes distinct metabolic pathways to
circumvent human mucosal defenses. We have applied this information to systems biology approaches to
generate a preliminary metabolic network reconstruction for Gc. This analysis leads to the prediction that Gc
utilizes specific host-derived metabolites to fuel its metabolism – in particular, lactate. PMNs are highly glycolytic
and consequently secrete lactate. Lactate can be consumed by Gc and is known to stimulate Gc glycolysis. Thus
we hypothesize that Gc exploits PMN metabolism, specifically lactate secretion, to survive at mucosal surfaces.
In this proposal, we will identify the central carbon metabolic pathways used by Gc in the presence of neutrophils,
using a combination of metabolite analysis, metabolic modeling, and bacterial genetic knockouts in Gc metabolic
enzymes. We will then test the necessity of these metabolic pathways in Gc for enhancing bacterial survival from
neutrophils and the underlying mechanisms, including modulating neutrophil antimicrobial responses, changing
Gc sensitivity to neutrophil antimicrobial components, and/or circumventing host nutritional immunity, or
modulating neutrophil antimicrobial responses. Together, this proposal will address key gaps in knowledge of
the fundamental metabolic processes of Gc during infection that are likely to have major impacts on outcomes
of gonorrhea.

## Key facts

- **NIH application ID:** 10364695
- **Project number:** 5R21AI161302-02
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Alison K Criss
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $201,875
- **Award type:** 5
- **Project period:** 2021-03-04 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10364695

## Citation

> US National Institutes of Health, RePORTER application 10364695, Neisseria gonorrhoeae central metabolism in the context of neutrophilic inflammation (5R21AI161302-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10364695. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*