# Mapping Protein Interaction Networks Essential for Gonococcal Pathogenesis

> **NIH NIH R01** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2022 · $628,605

## Abstract

Neisseria gonorrhoeae (Ngo) is the etiological agent of the sexually transmitted infection (STI) gonorrhea, a high
morbidity disease with ~100 million cases worldwide each year. Alarmingly, therapeutic and pharmacologic
approaches to treat gonorrhea are under threat by the global emergence of `superbug' strains resistant to all
clinically useful antibiotics. Gonococci are exquisitely adapted to life in humans, to the extent that they have shed
much of the metabolic capacity typical of other bacteria and depend upon unique strategies that allow for
replication and immune evasion while colonizing human mucosal tissues. Reflecting this specialization, Ngo
genomes encode less than half the number of proteins observed in more prototypical bacteria such as E. coli. A
biological enigma then is how the neisserial genome has evolved to exploit a variety of mucosal niches and how
strain variation contributes to pathogenesis. Our hypothesis is that this depends on specialized protein-protein
interaction networks, and that acquiring this knowledge will have major clinical value because it would reveal
protein complexes and processes uniquely required by gonococci but not commensal species, either because
they have distinct functional capabilities or because the smaller neisserial genome lacks functional redundancy
that allow other bacteria to overcome environmental or other stresses. The core goal of our multidisciplinary
research strategy is the generation of global protein interaction networks of gonococci that offer a detailed
systems-based understanding of the specialized cellular apparatus used by Ngo during infection. While
population genomic, transcriptional profiling and genetic screens have provided valuable insights into Ngo
biology, these studies would gain significant benefit through their integration with comprehensive roadmaps
detailing the organization of protein complexes that support growth and infection phenotypes. Key to the clinical
relevance of this project is a focus on the impact of strain variation through investigations of infectious clinical
isolates of Ngo, supported by complementary investigations of the population genomics of Ngo. We will combine
quantitative mass spectrometry, network analysis, comparative genomics and targeted mutagenesis with in vitro
and in vivo phenotype analysis to illuminate macromolecular protein assemblies that are critical to infection and
clinical persistence within the genital mucosa. By the end of this grant, we will have identified key conserved
components of the physical circuitry driving gonococcal growth, infection and adaptation to human mucosal
tissues, providing mechanistic insights into its unique pathobiology, and laying the foundation for future clinical
intervention strategies to combat infectious disease.

## Key facts

- **NIH application ID:** 10401945
- **Project number:** 5R01AI146941-02
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Andrew EMILI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $628,605
- **Award type:** 5
- **Project period:** 2021-05-06 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10401945

## Citation

> US National Institutes of Health, RePORTER application 10401945, Mapping Protein Interaction Networks Essential for Gonococcal Pathogenesis (5R01AI146941-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10401945. Licensed CC0.

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