# Copper is a Host Effector in Protection Against Urinary Tract Infection

> **NIH NIH R01** · TEXAS A&M AGRILIFE RESEARCH · 2020 · $344,058

## Abstract

The urinary tract, especially the bladder, is one of the most common sites of bacterial infection in
humans. Uropathogenic Escherichia coli (UPEC) is the predominant cause of urinary tract infection (UTI).
Women, children, the elderly, and individuals with catheters, uroliths, or diabetes mellitus are highly
susceptible to UTI. There is an immediate need for novel strategies to manage UTI because of an alarming
increase in antibiotic resistance in UPEC globally. We have demonstrated that copper (Cu) is mobilized to
urine as a host response during clinical UTI in patients. We have developed a non-human primate model of
UTI that recapitulates urinary Cu mobilization observed in human UTI. Our findings, taken together with reports
of fulminant UTI in patients with Menkes disease (who cannot absorb dietary Cu), highlight an important and
novel biological role for Cu in the protection against UTI. Our long-term research goal is to define the molecular
and cellular features of host-pathogen interaction during UTI to identify targets for therapeutic development.
Major objectives of this proposal are to define the mechanism of Cu-mediated protection against UPEC
colonization, and to determine how Cu is mobilized to urine during UTI. Based on our published and
preliminary data, we hypothesize that Cu is mobilized to urine in response to UPEC signals to impede
bacterial survival, and that augmenting the toxicity of Cu will promote UPEC clearance. The rationale for
the proposed work is that understanding Cu mobilization, and its impact on UPEC survival are critical to
develop therapeutics that bolster this innate response to resolve UTI. We will test our central hypothesis by
pursuing the following specific aims: 1) Determine how copper deters UPEC survival, and identify pathogen
signals that trigger copper mobilization; 2) Define the mechanism of copper-mediated UPEC killing within
human phagocytes; and 3) Determine the effect of augmenting the toxicity of copper on UPEC clearance. The
expected outcomes of this study include understanding the direct and indirect impact of Cu on UPEC
clearance during UTI, and the identification of the pathogen signals that trigger Cu mobilization. We will
determine the mechanism of Cu-mediated UPEC killing in human phagocytes. Cu-boosting treatments are
anticipated to promote UPEC clearance in the mouse and non-human primate models of UTI. The substantial
positive impact of this study will be elucidating the role of an innate host defense effector in protection against
UTI in humans. The proposed research is significant because our findings are anticipated to break new ground
to develop novel interventions against UTI. Our approach is innovative because we seek to bolster a host
effector that is amenable to dietary and pharmacological modulation, to promote resolution of UTI. In summary,
the proposed study is expected to confer a significant public health benefit against UTI, a ubiquitous and
profoundly painful infectious d...

## Key facts

- **NIH application ID:** 9920705
- **Project number:** 5R01DK114224-03
- **Recipient organization:** TEXAS A&M AGRILIFE RESEARCH
- **Principal Investigator:** Sargurunathan Subashchandrabose
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $344,058
- **Award type:** 5
- **Project period:** 2018-12-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9920705

## Citation

> US National Institutes of Health, RePORTER application 9920705, Copper is a Host Effector in Protection Against Urinary Tract Infection (5R01DK114224-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9920705. Licensed CC0.

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