# Fungal natural products targeting antimicrobial resistant Mycoplasma genitalium

> **NIH NIH R21** · UNIVERSITY OF OKLAHOMA · 2022 · $194,062

## Abstract

Sexually transmitted infections are a worldwide health concern, with over a million infections acquired each day.
Mycoplasma genitalium is an important sexually transmitted bacterial pathogen, associated with severe upper
reproductive tract sequelae in women and lower genital tract infections in both men and women. In November 2019,
the CDC convened a workshop focused on STD-related pelvic inflammatory diseases in which M. genitalium was
recognized as a key, but understudied, emerging pathogen that threatens the safety and welfare of the American
public. The prevalence of M. genitalium in the US is higher than Neisseria gonorrhoeae and Chlamydia trachomatis
in a growing number of settings with resistance to the recommended first-line treatment, azithromycin, exceeding
50% in many situation and reaching 70-90% in the most-at-risk populations. Alarmingly, resistance to moxifloxacin,
recommended for macrolide-resistant strains, is increasingly detected. This spurred the CDC to include M. genitalium
on its watch list in the “2019 Antibiotic Resistance Threats in the United States” report. New drugs are needed to
target what is clinically evolving into a nearly untreatable pathogen. We hypothesize that fungal natural products
are an untapped source of novel antimicrobials that can be used to target M. genitalium and propose to combine
our unique expertise in drug discovery and M. genitalium biology (one of only a few labs in the US that studies
this fastidious organism) to develop early-stage lead compounds. We will test this hypothesis and work toward
providing urgently needed bioactive drug leads through the following three specific aims: (1) test libraries of
fungus-derived pure compounds and extracts for inhibition of M. genitalium growth; (2) prioritize bioactive
substances, conduct assay-guided purification of inhibitory molecules, and determined their structures; and (3)
investigate the activity of bioactive substances against clinical strains, as well as test for resistance development.
Specifically, we will use a library of 900 purified fungal natural products, as well as 2,500 extracts produced from
taxonomically diverse fungi collected over a wide range of geographical and environmental sites for activity
against M. genitalium (strain G37 will be used as the assay sensor strain). Highly active pure compounds that
exhibit low levels of toxicity toward human cells will be further tested against a collection of low passage
antimicrobial-resistant M. genitalium clinical isolates. Upon characterizing the inhibition profiles of the active
compounds as bactericidal or bacteriostatic, the potential for resistance development will be probed. We
anticipate delivering 2-3 new bioactive natural-product scaffolds during each year of this R21 investigation with
the goal of identifying highly promising molecules that will become the subjects of further lead compound
development in the context of future R01 studies. We are unaware of prior focused efforts ...

## Key facts

- **NIH application ID:** 10308114
- **Project number:** 5R21AI153863-02
- **Recipient organization:** UNIVERSITY OF OKLAHOMA
- **Principal Investigator:** Robert Henry Cichewicz
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $194,062
- **Award type:** 5
- **Project period:** 2020-11-25 → 2023-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10308114

## Citation

> US National Institutes of Health, RePORTER application 10308114, Fungal natural products targeting antimicrobial resistant Mycoplasma genitalium (5R21AI153863-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10308114. Licensed CC0.

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