# Nitroimidazole susceptibility and mechanisms of resistance in Mycoplasma genitalium

> **NIH NIH R21** · UNIVERSITY OF WASHINGTON · 2024 · $233,250

## Abstract

PROJECT SUMMARY
 Mycoplasma genitalium is a sexually transmitted bacterial pathogen that frequently causes genital tract
syndromes including urethritis in men and cervicitis, pelvic inflammatory disease, and infertility in women.
Sensitive diagnostic tests have been approved in the US since 2019, however, few treatment options for M.
genitalium are available. M. genitalium lacks a cell wall and has only a single membrane so antibiotics
targeting peptidoglycan synthesis, or the bacterial outer membrane, are completely inactive. Doxycycline is
only 30-40% effective in eradicating M. genitalium infections. The efficacy of azithromycin, the preferred
therapy, has decreased in recent years and now more than 50% of US strains are resistant. In high-risk
populations in the US and worldwide azithromycin resistance reaches 100%. More than 10% of strains are
resistant to moxifloxacin, the recommended second line therapy, and resistance to both macrolides and
fluoroquinolones is increasingly reported. No effective treatment options are approved in the US to treat these
dually resistant infections. In addition, moxifloxacin is not approved for certain patient groups (e.g., pregnant
women, adolescents <18 years old), and the FDA discourages fluoroquinolone use unless no other options
exist because of potentially severe and permanent side effects. There is an urgent and immediate need to
identify additional therapies with activity against M. genitalium. We determined that M. genitalium is susceptible
in vitro to nitroimidazoles, consistent with a recently published clinical trial demonstrating that metronidazole
reduced M. genitalium infection in women with PID, and contrary to the accepted view that these drugs are
inactive against mycoplasmas. Building on our preliminary data we now propose to define the activity of
nitroimidazole and nitrofuran antibiotics against M. genitalium in detail. We will assess the in vitro susceptibility
to more than a dozen nitro group-containing drugs for which clinical safety and efficacy data are known,
including several that are approved for other indications in the US and elsewhere in the world. The in vitro
activity of these drugs will be compared in terms of minimum inhibitory concentration, time kill kinetics, post
antibiotic effect, activity against biofilms, and spontaneous resistance rates to inform future clinical trials.
Differences in strain susceptibility will be determined by measuring the potency of top performing analogs
against our existing collection of clinical isolates. We found that nitroimidazole resistance is associated with
mutations affecting an oxidoreductase gene suggesting a mechanism for the bioreductive activation of the
prodrug that is necessary for its bactericidal activity. We propose to expand and confirm these findings by
isolating additional resistant mutants and defining drug-enzyme interactions with wild type and mutant alleles of
the purified oxidoreductase. This study will have direct tra...

## Key facts

- **NIH application ID:** 10785739
- **Project number:** 1R21AI180339-01
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Gwendolyn Wood
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $233,250
- **Award type:** 1
- **Project period:** 2024-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10785739

## Citation

> US National Institutes of Health, RePORTER application 10785739, Nitroimidazole susceptibility and mechanisms of resistance in Mycoplasma genitalium (1R21AI180339-01). Retrieved via AI Analytics 2026-08-23 from https://api.ai-analytics.org/grant/nih/10785739. Licensed CC0.

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