# Survival of Neisseria gonorrhoeae after primary human neutrophil challenge

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2020 · $551,645

## Abstract

PROJECT SUMMARY/ABSTRACT
 Neisseria gonorrhoeae (Gc) is an obligate human bacterial pathogen and the cause of gonorrhea. Gc is a
major public health concern because numbers of cases remain high, it has gained resistance to multiple
antibiotics, no vaccine exists, and infection is associated with debilitating, lifelong negative outcomes such as
infertility and ectopic pregnancy. Mucosal colonization by Gc drives the recruitment of polymorphonuclear
leukocytes (PMNs or neutrophils) to the site of infection and the production of a characteristic purulent
exudate. Despite PMNs’ robust phagocytic and antimicrobial activities, infectious Gc can be cultured from
PMN-rich exudates, implying Gc possesses mechanisms to evade killing by PMNs. The failure of PMNs to
clear Gc not only allows the infection to persist, but also sustains the PMN inflammatory response, causing the
tissue damage that underlies infertility and other sequelae. To identify the mechanisms used by Gc to resist
killing by PMNs, we developed an infection model using adherent, chemokine-treated primary human PMNs to
approximate the physiological state of PMNs recruited to mucosal surfaces. We used this model to uncover
two major ways in which Gc survives after exposure to PMNs. First, Gc expresses gene products that confer
resistance to PMN antimicrobial compounds, such as proteases and antimicrobial peptides. Second, Gc varies
expression of surface structures to modulate the route of phagocytosis by PMNs and consequent exposure to
these compounds. Specifically, Gc that have phase-varied off expression of opacity-associated (Opa) proteins
is internalized into immature phagosomes in which it survives and suppresses the PMN oxidative burst, while
Gc expressing an Opa protein that interacts with carcinoembryonic antigen-related cell adhesion molecules
(CEACAMs) 1 and 3 is phagocytosed into a mature, degradative phagolysosome and induces a potent
oxidative burst. In this renewal proposal, we will continue to dissect the mechanisms that underlie Gc survival
after PMN challenge. Aim 1 will define how Opa-negative Gc is phagocytosed into PMNs without eliciting the
oxidative burst or phagolyososome formation and will evaluate the survival profile of Gc expressing an Opa
protein that does not bind CEACAM3. We will evaluate the long-term consequences of these receptor-
mediated interactions on the viability of both Gc and PMNs. Aim 2 will build upon results from a Tn-seq
experiment conducted in the previous funding period to examine how bacterial efflux pumps and
lipooligosaccharide variants contribute to Gc survival from PMNs. All experiments will be conducted with the
adherent, interleukin-8 treated PMN infection model alongside analysis of freshly collected human gonorrheal
exudates. Together, the results from this research will reveal the diverse approaches used by Gc to survive
from PMNs, which ensures the continued persistence of gonorrhea in the human population even when facing
a neutrophil...

## Key facts

- **NIH application ID:** 9812827
- **Project number:** 5R01AI097312-08
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Alison K Criss
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $551,645
- **Award type:** 5
- **Project period:** 2012-07-01 → 2022-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9812827

## Citation

> US National Institutes of Health, RePORTER application 9812827, Survival of Neisseria gonorrhoeae after primary human neutrophil challenge (5R01AI097312-08). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9812827. Licensed CC0.

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