# Admin Supplement for Elucidating the Orchestrated Bacterial Response to Copper and Zinc Toxicity

> **NIH GM R35** · UNIVERSITY OF ARIZONA · 2026 · $89,590

## Abstract

PROJECT SUMMARY
Metal dysbiosis is detrimental to any living system as approximately 40% of proteins use metals as a cofactor
or structural component. Therefore, when pathogenic bacteria invade a host, there is a battle for metal
micronutrients such as iron, calcium, manganese, and zinc that benefit each organism. While human hosts
acquire metals through their diet, bacteria must acquire metals from within the host. However, for bacteria that
exist at the host/pathogen interface, some host-utilized metals can be toxic to bacteria. For example, compared
to iron, calcium, and manganese concentrations needed for survival, zinc and especially copper are toxic to
bacteria even at lower concentrations. As such, bacteria have evolved import and export systems to maintain
homeostasis. Complicating metal acquisition is mismetallation, when the unintended metal binds to the protein
to diminish function (e.g., low enzymatic turnover or decreased substrate binding), specifically because the
stability of complex formation with divalent metal is as follows: Cu >Zn > Fe > Mn > Ca. The human host
sequesters beneficial metals (iron, calcium, and manganese) to restrict infection while also bombarding the
bacteria with zinc and copper. How bacteria respond to copper + zinc stress and the different concentrations of
these metals they encounter in the host are largely unknown. While metal toxicity has been the subject of other
studies, most of these have focused on single concentrations of one metal, often in complex media. These
media are more lavish than the host environment and may mask portions of the metal response. To address
fundamental gaps in knowledge regarding how bacteria respond to metal dysbiosis, we used a multi-omics
approach (transcriptomics, metabolomics, and suggest a proteomic arm) to investigate the pathways affected
during bacterial disruption via copper and zinc at varying concentrations in a host-adjacent, minimal, and
defined media in Streptococcus pneumoniae as

## Key facts

- **NIH application ID:** 11405276
- **Project number:** 3R35GM128653-07S1
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** Michael David Leslie Johnson
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** GM
- **Fiscal year:** 2026
- **Award amount:** $89,590
- **Award type:** 3
- **Project period:** 2018-07-01T00:00:00 → 2029-06-30T00:00:00

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11405276

## Citation

> US National Institutes of Health, RePORTER application 11405276, Admin Supplement for Elucidating the Orchestrated Bacterial Response to Copper and Zinc Toxicity (3R35GM128653-07S1). Retrieved via AI Analytics 2026-07-06 from https://api.ai-analytics.org/grant/nih/11405276. Licensed CC0.

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