# Study of Neisseria gonorrhoeae adaptability to impact microbial survival and host response inside human neutrophil phagosomes

> **NIH NIH K08** · UNIVERSITY OF IOWA · 2020 · $187,488

## Abstract

Neisseria gonorrhoeae (Ng) is an intracellular and exclusively human pathogen that causes the sexually
transmitted disease gonorrhea. A hallmark of gonorrhea is the exuberant inflammation secondary to
recruitment of human polymorphonuclear leukocytes (hPMN). Under normal circumstances, hPMN ingest and
kill invading microbes inside hPMN phagosomes, after which spent hPMN undergo phagocytosis-induced cell
death (PICD) as part of the programmed resolution of inflammation (1, 2). As a successful pathogen, Ng not
only survives and replicates inside hPMN phagosomes, but also delay PICD of hPMN (3, 4). How Ng
undermines normal hPMN-mediated host defense by surviving hPMN killing and delaying PICD of hPMN has
not been elucidated.
The candidate’s objective is to understand the mechanisms underpinning the adaptability of Ng inside hPMN
phagosomes. The candidate’s hypotheses are that (1) that acetylation is one of the post-translational
modifications of neisserial proteins that is critical to Ng survival and (2) that the Ng escape from phagosomes
and modification of hPMN signaling pathways delay programmed cell death of hPMN that normally follows
phagocytosis. To test these hypotheses, the candidate has created two specific aims:
Aim 1: To determine the role of Ne-lysine acetylation as a regulatory determinant for the survival of Ng
inside hPMN phagosomes.
Aim 2: To determine the effect of NGAG00012 on hPMN phagosomes and subsequent cell fate of hPMN
fed Ng.
This proposal is innovative because the candidate uses biased (mutagenesis and mass spectrometry) and
unbiased (transcriptome analysis) approach to elucidate Ng biology within the phagosomes of hPMN, a
clinically relevant context. The rise in resistance of Ng to antibiotics has made effective treatment for gonorrhea
nearly impossible, thus making it imperative to understand Ng’s behavior inside hPMN. This proposal is
significant in that its discoveries will provide better understanding of how Ng inside hPMN phagosomes
survives and thus a rational for novel therapeutic intervention for gonorrhea.

## Key facts

- **NIH application ID:** 9889262
- **Project number:** 1K08AI143799-01A1
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Christine Cho
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $187,488
- **Award type:** 1
- **Project period:** 2020-02-15 → 2020-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9889262

## Citation

> US National Institutes of Health, RePORTER application 9889262, Study of Neisseria gonorrhoeae adaptability to impact microbial survival and host response inside human neutrophil phagosomes (1K08AI143799-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9889262. Licensed CC0.

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