# Diversity Supplement to Immune Evasion Mechanisms of Mycoplasma genitalium V

> **NIH NIH R21** · UNIVERSITY OF WASHINGTON · 2021 · $20,269

## Abstract

PROJECT SUMMARY
Mycoplasma genitalium (MG) is a sexually-transmitted, reproductive tract pathogen of men (urethritis) and
women (cervicitis, pelvic inflammatory disease, ectopic pregnancy, infertility) with a similar, or higher,
prevalence as compared to Chlamydia trachomatis and Neisseria gonorrhoeae. Antibiotic resistance is
increasing in MG isolates, with some infections totally untreatable with recommended regimens in the US. MG
was included on the Watch List of the CDC 2019 Antimicrobial Threat Report, and was recognized as an
understudied cause of PID at the November 2019 workshop “New frontiers in STD-related pelvic inflammatory
disease (PID), infertility, and other sequelae”. The recent FDA approval of two MG diagnostic tests (Hologic
and Roche) will certainly increase public awareness of MG, and demands for improved treatments. Our
laboratory has focused on understanding the ability of MG to persist for weeks to years despite the presence of
specific antibodies in the genital tract, the variability of the immunodominant MgpB and MgpC adherence
proteins, and the local and systemic antibody response to these proteins during infection. We demonstrated
that MgpB and MgpC undergo phase and antigenic variation via a unique system of recombination between
the mgpBC expression site and partial copies archived in the chromosome. In the parent grant (R21AI148816-
01), we extend these studies to define the epitopes and the consequences of antibody binding to the
conserved and variable regions of MgpC. Further, we define the role of the newly identified MG281 antibody
binding protein in evasion of the innate and specific immune response including binding to non-specific IgG
and IgA, effect on MG complement resistance, and the effect of MG281 antibody binding on opsonophagocytic
killing of MG. With this supplement application, we propose to expand Aims 2 and 3 of the parent award
to identify domains within MG281 important for the function(s) of this unique antibody binding protein.
As the structures of multiple MG281-Fab cocrystals are known, a series of precise, rationally-designed
deletion and amino acid substitution mutations will be constructed and their effect on MG281 function
measured in terms of antibody binding, resistance to antibody-mediated complement killing, and
phagocytosis of MG. We hypothesize that MG281 protects MG from attack by innate immune defenses of the
genital tract early in infection. As MgpB and MgpC are the dominant antigens targeted by patient antibodies,
we further hypothesize that MG281 protects MG against killing by specific antibodies by preventing
complement attack and opsonophagocytosis by genital tract immune cells. These experiments, along with our
novel approaches pioneering experimental methods for the difficult field of mycoplasma research, will inspire
improved prevention strategies to combat this increasingly antibiotic-resistant and important pathogen and
provide a unique opportunity for undergraduate resear...

## Key facts

- **NIH application ID:** 10134121
- **Project number:** 3R21AI148816-02S2
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Gwendolyn Wood
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $20,269
- **Award type:** 3
- **Project period:** 2020-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10134121

## Citation

> US National Institutes of Health, RePORTER application 10134121, Diversity Supplement to Immune Evasion Mechanisms of Mycoplasma genitalium V (3R21AI148816-02S2). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10134121. Licensed CC0.

---

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