# A Synthetic Approach for Bacterial-Mammalian Cell Binding

> **NIH NIH R21** · UNIVERSITY OF CINCINNATI · 2020 · $245,041

## Abstract

Project Summary
Synthetic biology and advances in molecular biology have transformed the field of genetic engineering,
particularly in the context of adding new function to cells and organisms. Genetic manipulation of bacteria has
opened new opportunities to address old and emerging biomedical problems. To harness the full potential of
these genetically engineered bacteria in the biomedical domain, new tools to detect and track them in vivo are
required. Molecular imaging is advantageous over traditional diagnostic tools because it enables identification
and tracking of these bacteria in the host environment in real-time. However, current imaging contrast agents
are non-specific, non-selective and typically identify “dead” bacteria. In this proposal we propose to use
bacterial siderophores, metal binding molecules secreted by bacteria that bind to distinct receptors on bacterial
membrane, as contrast agents for nuclear imaging. Bacterial siderophores have evolved to serve as metal
chelators for a wide variety of metals with the majority showing a high binding affinity for iron. Siderophores are
considered “gateways” into the bacterial cell and have often been exploited as a ‘Trojan horse’ strategy to
deliver drugs against antibiotic-resistant bacteria. The proposed strategy to deliver radionuclides such as 64Cu
using this pathway will enable molecular imaging of a diverse array of wildtype and engineered bacteria in a
siderophore-specific manner. In Aim 1 we will determine the in vivo stability and targeting ability of
metallophore/64Cu complexes to locate static wildtype bacteria . In Aim 2 we will engineer E.coli Nissle to
express GFP binding surface nanobodies to bind to metastatic cancer cells expressing surface GFP and
evaluate the targeting ability of metallophore/64Cu complexes to these engineered bacteria. We will evaluate
whether the tracers can track down the engineered bacteria at unique niches in the body and assess its
functional stability at the same time. We will optimize and develop a quantitative nuclear imaging method that
can detect “live” bacteria and the lesions when they are significantly smaller than those currently detected with
existing diagnostic tests and imaging methods. Compared to traditional techniques used to manufacture
probes, this strategy seeks to simplify the process considerably by combining the function of metal attachment
and cell recognition into a single molecule. If successful, it will enable creation of new knowledge about
metallophore-metal, metallophore-bacteria, metallophore-host and bacteria-host interactions in living systems
that would help create advanced tools and strategies.

## Key facts

- **NIH application ID:** 9959062
- **Project number:** 1R21GM137321-01
- **Recipient organization:** UNIVERSITY OF CINCINNATI
- **Principal Investigator:** Nalinikanth Kotagiri
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $245,041
- **Award type:** 1
- **Project period:** 2020-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9959062

## Citation

> US National Institutes of Health, RePORTER application 9959062, A Synthetic Approach for Bacterial-Mammalian Cell Binding (1R21GM137321-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9959062. Licensed CC0.

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