# Elucidating Molecular-Level Roles of Essential Metals in Gut Bacteria with New Fluorescent Protein-Based Metal Ion Sensors

> **NIH NIH R35** · UNIVERSITY OF HOUSTON · 2020 · $387,083

## Abstract

PROJECT SUMMARY
 Dietary changes in metal nutrients, including zinc and iron, influence the composition of the microbiota
and correlate with increased infection susceptibility and gastrointestinal diseases, but the molecular mechanisms
underlying these effects remain largely unknown. This lack of knowledge severely limits our ability to predict how
diet or host metal status will impact treatment of gastrointestinal diseases or infection. Our long-term goal is to
elucidate the molecular mechanisms governing how essential metals affect the human gut microbiota. The
overall objective of the proposed work is to determine how essential metals affect growth and communication
within probiotic bacterial communities of Lactobacillus species. Our research strategy is 1) to develop and apply
protein-based fluorescent sensors that do not rely on oxygen and 2) to uncover molecular mechanisms through
which metal ions affect gut microbiota homeostasis. Oxygen-insensitive protein-based fluorescent sensors will
be used in live anaerobic cultures containing Lactobacillus to study metal uptake and how metal ion levels vary
over time. Pure, multispecies, and in vitro gut model cultures will be used to evaluate how metal ion homeostasis
varies with additional bacterial species and increasing complexity. Beyond direct detection and tracking of
essential metals in culture with fluorescent sensors, we are carrying out systematic studies to measure how
changes in essential metals affect Lactobacillus physiology and cell-cell communication (quorum sensing). Here,
we are investigating the capacity of Lactobacillus species to store excess metal ions and aiming to identify the
genes affected by varied metal levels in growth cultures. We are also measuring how varied metal levels affect
the abundance of Lactobacillus quorum sensing signaling molecules. This research program is enhanced by
collaborations with experts in microbiology, microbiome, and advanced fluorescence microscopy. The research
is significant because it will provide mechanistic insight to how dietary metals affect gut microbiota composition
and function. This insight is important because it will be useful for predicting the effects of metal-based dietary
interventions and could potentially identify new targets to mitigate these effects. Furthermore, it will provide a
knowledge basis for probiotic dietary interventions to combat gastrointestinal diseases and potentially identify
new drug targets. The research is innovative because it represents a substantive departure from current work
by shifting focus to uncover molecular-level mechanisms and roles for metal ions in gut bacteria that affect
microbiota composition and function. By studying the Lactobacillus genus, we take advantage of well-established
genetic approaches while focusing on an abundant organism in the small intestine, where most metal nutrient
uptake occurs. Furthermore, Lactobacillus are well accepted as probiotics, but much remains to be learn...

## Key facts

- **NIH application ID:** 10029435
- **Project number:** 1R35GM138223-01
- **Recipient organization:** UNIVERSITY OF HOUSTON
- **Principal Investigator:** Melissa Lynn Zastrow
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $387,083
- **Award type:** 1
- **Project period:** 2020-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10029435

## Citation

> US National Institutes of Health, RePORTER application 10029435, Elucidating Molecular-Level Roles of Essential Metals in Gut Bacteria with New Fluorescent Protein-Based Metal Ion Sensors (1R35GM138223-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10029435. Licensed CC0.

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