# Interferometry to understand beta-lactam heteroresistance

> **NIH NIH R35** · GEORGIA INSTITUTE OF TECHNOLOGY · 2023 · $126,530

## Abstract

The World Health Organization (WHO) has highlighted antibiotic resistance as one of the greatest medical
challenges of the 21st century. Choosing effective antibiotics is therefore critical, and basing antibiotic selection
on bacterial susceptibilities potentially offers the greatest therapeutic benefit. Current antibiotic susceptibility
tests are unable to detect a common form of resistance (present in more than 25% of antibiotic-bacteria
combinations) known as heteroresistance, in which a minor subpopulation of bacterial cells is phenotypically
resistant. These resistant cells rapidly expand in the presence of an antibiotic and thus can cause treatment
failure. Developing a new susceptibility test is further complicated by the requirements of the clinical microbiology
laboratory; to be adopted, a susceptibility test must require minimal manual labor, work robustly, and be
inexpensive – properties that are often at odds with high sensitivity. Based on these issues, there is broad
agreement that a new technological approach is required.
In the parent grant, we proposed to develop a new susceptibility test using interferometry to measure bacterial
population topography. The use of interferometry to measure topography has no precedence in antibiotic
susceptibility testing, and little precedence in biomedical research in general. However, it is common in physics
and materials science as it is rapid, doesn’t require dyes or stains, and provides super-resolution measurements
of topography. Interferometers are inexpensive and robust. In exciting preliminary results, we have demonstrated
that with interferometry we can detect heteroresistance in 2 hours, and even distinguish low levels of
heteroresistance from susceptibility.
In this equipment supplement, we are requesting funds to purchase another interferometer. In the process of
developing an interferometry-based susceptibility test, we made a discovery about the biophysics of beta-lactam
heteroresistance. In line with the parent grant’s proposed work on measuring and understanding bacterial
topography, as well as proposed work on interferometry-based diagnostics, here we propose to investigate how
the growth of beta-lactam resistant cells depends on the local concentration of resistant cells. These experiments
are necessarily long (each takes at least 24 hours) and drawing conclusions will require testing many different
strains against different beta-lactams, and thus require additional equipment.
This project addresses fundamental questions about the biophysics of rare resistant cells. Further, as beta-
lactams are the most used class of antibiotics, the results of the work proposed here will also hold clinical
relevance.

## Key facts

- **NIH application ID:** 10798548
- **Project number:** 3R35GM138354-04S1
- **Recipient organization:** GEORGIA INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Peter Yunker
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $126,530
- **Award type:** 3
- **Project period:** 2020-09-15 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10798548

## Citation

> US National Institutes of Health, RePORTER application 10798548, Interferometry to understand beta-lactam heteroresistance (3R35GM138354-04S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10798548. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*