# Siderophore-like molecules from the opportunistic fungal pathogen Candida albicans

> **NIH NIH F32** · JOHNS HOPKINS UNIVERSITY · 2020 · $69,018

## Abstract

PROJECT SUMMARY
Microbial pathogens are faced with unique challenges when acquiring metal micronutrients within a host. As
part of innate immune defenses, hosts attempt to starve pathogens of metals in a process called nutritional
immunity. One mechanism microbes use to overcome this barrier is to secrete small, metal binding compounds
called metallophores (<1.5 kDa) that help scavenge these essential micronutrients. The majority of
metallophores described to date are specific for Fe and are called siderophores. Bacteria make a wide
assortment of metallophores through various biosynthetic pathways, but only a single biosynthetic pathway for
siderophores has been described for fungi. Interestingly, some fungal pathogens like Candida albicans lack
this biosynthetic pathway for fungal siderophores, but nevertheless have siderophore receptors. To date no
metallophore has been identified for C. albicans. C. albicans is an important opportunistic fungal pathogen and
requires metals to survive in the host. My preliminary data suggests that C. albicans does secrete
metallophore-like compounds (MLCs) based on their low molecular weight (<1 kDa) and metal binding
properties (can bind both Fe and Cu). One of these MLCs, (MLC1) is induced by Fe starvation indicative of a
role in Fe homeostasis. We hypothesize that C. albicans produces its own metallophores under metal-
starvation conditions and that these are distinct from those produced by other fungi. To investigate this
hypothesis, I will pursue the following aims. Aim1. Chemical identification of putative metallophores in C.
albicans. To determine the chemical structure of the MLCs, I will first purify the MLCs to homogeneity using
HPLC. I will then use high resolution MS/MS and NMR to determine the functional groups, chemical structure
and metal-binding specificities of the MLCs. Aim 2. Characterize the function and synthesis of C. albicans
metallophore-like compounds. After identifying the chemical structure of these small metal-binding compounds,
I will determine the physiological conditions that regulate their production including both metal starvation and
metal excess. I will also test whether MLC1 can act as a source of Fe for C. albicans, and whether the known
siderophore receptor is required for this process. Finally, I will try to determine the genes involved in the
production of these MLCs using the structural information from Aim 1 in combination with transcriptional data
obtained from an RNA seq experiment looking for genes expressed under Fe starvation conditions. Together
these experiments propose to identify and characterize the first metallophore for C. albicans.

## Key facts

- **NIH application ID:** 9990272
- **Project number:** 1F32GM137469-01
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Natalie Robinett
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $69,018
- **Award type:** 1
- **Project period:** 2020-06-01 → 2021-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9990272

## Citation

> US National Institutes of Health, RePORTER application 9990272, Siderophore-like molecules from the opportunistic fungal pathogen Candida albicans (1F32GM137469-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9990272. Licensed CC0.

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