# Uncovering the evolutionary history of bacterial endosymbiosis in opportunistic fungal pathogens of humans

> **NIH NIH R21** · CORNELL UNIVERSITY · 2024 · $220,359

## Abstract

PROJECT SUMMARY
The goal of this exploratory work is to elucidate the evolutionary history of symbiotic associations between the
Mucoromycotina fungi and their endosymbiotic bacteria (EB), focusing on population-level processes, including
fungal adaptation to human hosts and contributions of shared 6-methyladenine (6mA) DNA epigenetic
modifications as means of communication between the partners. We expect that this work will establish
foundations for future treatment of mucormycoses, which are human infections caused by Mucoromycotina.
Mucormycoses are increasingly frequent, highly destructive, and often fatal in immune-compromised
individuals. While bacteria-free asymbiotic Mucoromycotina are responsible for many infections, EB are often
detected in clinical isolates and known to affect Mucoromycotina virulence in humans. Therefore, elucidating
population-level processes that govern these Mucoromycotina-EB symbioses is important for developing novel
mucoromycosis therapies. One of the mechanisms contributing to the establishment and maintenance of such
symbioses may be sharing of 6mA DNA modifications by Mucoromycotina and bacteria. Importantly, these
modifications and the contributing enzymes are nearly absent from mammals and potentially could be targeted
by pharmacological inhibitors for mucormycosis therapy.
To test the hypothesis that EB manipulate their fungal hosts through epigenomic reprogramming, we propose
functional characterization of candidate bacterial symbiosis factors, including adenine-specific DNA
methyltransferases. To gain insights into population-level processes shaping fungal-bacterial symbioses, we
plan to conduct a population genomic study of a model fungal-bacterial symbiosis complemented by a
population-level analysis of genome-wide 6mA modification and transcriptional landscapes in fungi differing in
the symbiotic status and source of isolation (natural versus clinical settings).
Expected outcomes of the project include insights into population-level processes, including fungal adaptation
to mammalian hosts and the role of epigenetic reprogramming in the initiation and functioning of fungal-
bacterial symbioses important for human health as well as 6mA methylome data for a leading causal agent of
mucormycosis. The findings are expected to be instrumental in developing future mucormycosis therapies
relying on 6mA DNA modification inhibitors.

## Key facts

- **NIH application ID:** 10988390
- **Project number:** 1R21AI180695-01A1
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** Teresa E Pawlowska
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $220,359
- **Award type:** 1
- **Project period:** 2024-06-12 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10988390

## Citation

> US National Institutes of Health, RePORTER application 10988390, Uncovering the evolutionary history of bacterial endosymbiosis in opportunistic fungal pathogens of humans (1R21AI180695-01A1). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10988390. Licensed CC0.

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