# Next generation tools for imaging bacterial infection and its relationship to the immune system

> **NIH NIH DP5** · UNIVERSITY OF PENNSYLVANIA · 2020 · $402,500

## Abstract

One of the great challenges of modern biomedical research is observing biologic
phenomena in animals and people. An important example of this is our limited ability to monitor
the course of bacterial infection. An image-based readout of a bacterial infection would allow
differentiation of infection from other etiologies, a tailored duration of antibiotic treatment, and
identification of antibiotic resistance suggesting an appropriate class of antibiotic.
 In addition to the clinical and population implications of improved monitoring of bacterial
infections, basic researchers do not have simple tools to measure the immune response to the
site of a bacterial infection. Again, imaging is suited to address this problem by facilitating in vivo
monitoring over space and time. My work seeks to develop imaging-based chemical and
synthetic biology technologies that illuminate bacterial pathogenesis, response to antibiotics, the
development of antibiotic resistance, and bacterial interactions with the immune system. I
propose complementary approaches to accomplish these goals using immune cells delivered
into the blood stream that track bacterial biomarkers –including bacterial surface markers and
bacterial enzymes– and using direct bacterial imaging with positron emission tomography
(PET). These new approaches leverage concepts and techniques I have developed including
“cell-cell proximity reporters”, protein destabilizing domains, and PET imaging based on the
antibiotic trimethoprim (TMP). Advantages of using immune cells include the ability to generate
multiplexed sensors and reporter outputs, transcriptional and enzymatic signal amplification,
and regional assessment of immune cell trafficking. An advantage of direct bacterial imaging is
the ability to image the bacterial load that does not depend on immune cell access to the
infection. The primary objectives of this proposal are 1) to develop new receptors that can report
the severity and species of bacterial infection in vivo. 2) to develop new classes of caged small
molecules for monitoring immune cell-bacterial cell interactions using synthetic biology
principles, and 3) to evaluate a new class of PET radiotracers I recently developed for imaging
infection in a rat model of cystic fibrosis (CF) and measure bacterial radiotracer uptake in
patients with CF before and after antibiotics.
 This work builds a foundation to monitor pathologic bacteria in vivo and spans from
bench to bedside. I expect to provide sets of reagents to the scientific community including
plasmids encoding receptors for a variety of bacteria, enzyme activated small molecules, and
useful PET probes, all geared toward specific imaging of live bacteria.

## Key facts

- **NIH application ID:** 10001362
- **Project number:** 5DP5OD026386-03
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Mark A Sellmyer
- **Activity code:** DP5 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $402,500
- **Award type:** 5
- **Project period:** 2018-09-17 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10001362

## Citation

> US National Institutes of Health, RePORTER application 10001362, Next generation tools for imaging bacterial infection and its relationship to the immune system (5DP5OD026386-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10001362. Licensed CC0.

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