# Antigenic variation of Mycoplasma genitalium during persistent genital tract infection of pig-tailed macaques

> **NIH NIH R21** · UNIVERSITY OF WASHINGTON · 2022 · $233,250

## Abstract

PROJECT SUMMARY
Mycoplasma genitalium (MG), a sexually transmitted bacterial pathogen, is increasingly recognized as a
significant public health concern. The prevalence of MG ranges from 1-4% in population-based studies to more
than 20% in patients at high risk of acquiring sexually transmitted infections. The disease spectrum of MG is
similar to Neisseria gonorrhoeae and Chlamydia trachomatis, and includes urethritis in men and cervicitis in
women. Of particular concern, MG infection is associated with serious upper reproductive tract sequelae in
women including pelvic inflammatory disease, infertility, preterm birth, and spontaneous abortion. Alarmingly,
antimicrobial resistance in MG is increasing: 40-100% of strains are completely resistant to azithromycin and
some infections are totally untreatable with US approved therapies. The recent FDA approval of two MG
diagnostic tests will certainly increase public awareness of MG and demands for improved treatment. An
animal model is urgently needed to understand the naturally history of MG infection including mechanisms of
persistence and immune evasion, studies that are difficult in patients given the imperative to treat symptomatic
infection. We have optimized our pig-tailed macaque model of persistent genital tract infection and now
propose to use this model to study the role of antigenic variation in immune avoidance. Extending our previous
work defining mechanisms of antigenic and phase variation of the immunodominant MgpB and MgpC adhesin
proteins, we will determine if variation is required for persistence in the genital tract. First, using whole genome
sequencing we will correlate the appearance of variants during 18 weeks of infection with the appearance of
antibodies specific to MgpB and MgpC in three MG-infected primates and archived specimens from prior
primate experiments. Second, the ability of the identical vs variant strain to re-infect animals that clear genital
tract infection will be assessed in order to understand strain specific immunity. Third, a non-variable, “locked”
MG strain that is unable to undergo antigenic variation will be constructed and characterized in vitro. Three
primates will be inoculated cervically with a mixed inoculum of wild type and “locked” MG to compare the
persistence and upper tract ascension of the two strains simultaneously over the 18 weeks of our model. All
infected primates will undergo necropsy to examine the cervix, uterus, and Fallopian tubes for gross pathology
and histology, and to assess the presence of MG in the upper reproductive tract. These experiments will not
only determine if gene variation is required for persistence but will also provide additional observations in
individual primates of the natural history of lower tract persistence, upper tract ascension, and immune
response (including cytokines, cellular infiltrates and antibodies specific for conserved and variable MG
antigens). These proposed experiments are highly significant in...

## Key facts

- **NIH application ID:** 10350240
- **Project number:** 1R21AI166005-01
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Gwendolyn Wood
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $233,250
- **Award type:** 1
- **Project period:** 2021-11-01 → 2023-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10350240

## Citation

> US National Institutes of Health, RePORTER application 10350240, Antigenic variation of Mycoplasma genitalium during persistent genital tract infection of pig-tailed macaques (1R21AI166005-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10350240. Licensed CC0.

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