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Development of a Rapid Antibiotic Susceptibility Test Capable of Detecting Heteroresistance

Award Number: R35GM138354
ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/15/2020
PERIOD OF PERFORMANCE END DATE: 06/30/2026

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Development of a Rapid Antibiotic Susceptibility Test Capable of Detecting Heteroresistance - The World Health Organization (WHO) has highlighted antibiotic resistance as one of the greatest medical challenges of the 21st century. Without new antibiotics, it is predicted that antibiotic resistant infections will cause 10 million annual deaths worldwide by the year 2050 (surpassing cancer). These infections are poised to negate many advances of modern medicine that rely on antibiotics. Thus, choosing effective antibiotics based on bacterial susceptibilities would provide the greatest therapeutic benefit. One form of resistance that is overwhelmingly undetected is 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. As heteroresistance is common (>25% of antibiotic-bacteria combinations), detecting heteroresistance is critical to address the growing crisis of antibiotic resistance. Indeed, it was recently demonstrated that knowledge of heteroresistance can be used to guide successful combination therapy, and can thus even treat pan-resistant bacteria. Unfortunately, clinical susceptibility tests lack the resolution to identify heteroresistance, and the laboratory test for heteroresistance is time consuming and slow. Further, the next-generation susceptibility tests currently under development are largely focused on rapid diagnostics performed on a small number of cells, making detection of rare cells impossible. 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. Here the development of a new, more sensitive susceptibility test using interferometry to measure bacterial population topography is proposed. The use of interferometry to measure topography has no precedence in antibiotic susceptibility testing, and little precedence in biomedical research. However, its commonly used in physical sciences as it is rapid, inexpensive, robust, doesn’t require dyes or stains, and provides super-resolution measurements of topography. Preliminary results demonstrate that interferometry has the resolving power to rapidly detect heteroresistance and distinguish it from susceptibility. Our interferometry-based approach is a substantial improvement over clinical susceptibility tests that cannot detect heteroresistance, research laboratory tests that can detect heteroresistance but are too slow for clinical application, and traditional topographic imaging approaches, e.g. confocal microscopy, that are expensive and lack the resolving power to distinguish heteroresistance from susceptibility. Building off our promising preliminary results, this proposal will determine the underlying biophysics relating bacterial topography to death and reproduction. This work is pivotal to reliably convert topography into susceptibility profiles across a broad range of clinically relevant bacteria and antibiotics.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2024	GEORGIA TECH RESEARCH CORP	926 DALNEY ST NW	ATLANTA	GA	30318	FULTON	USA	Biomedical Research and Research Training	000	5	8/5/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $302,504 )
2024	2024	GEORGIA TECH RESEARCH CORP	926 DALNEY ST NW	ATLANTA	GA	30318	FULTON	USA	Biomedical Research and Research Training	000	5	7/9/2024	NON-COMPETING CONTINUATION	$302,504
														Subtotal = $302,504

Issue Date FY: 2023 ( Subtotal = $429,034 )
2023	2023	GEORGIA TECH RESEARCH CORPORATION	926 DALNEY ST NW	ATLANTA	GA	30332	FULTON	USA	Biomedical Research and Research Training	001	4	7/19/2023	SUPPLEMENT FOR EXPANSION	$126,530
2023	2023	GEORGIA TECH RESEARCH CORPORATION	926 DALNEY ST NW	ATLANTA	GA	30332	FULTON	USA	Biomedical Research and Research Training	000	4	6/20/2023	NON-COMPETING CONTINUATION	$302,504
														Subtotal = $429,034

Issue Date FY: 2022 ( Subtotal = $302,504 )
2022	2022	GEORGIA TECH RESEARCH CORPORATION	926 DALNEY ST NW	ATLANTA	GA	30332	FULTON	USA	Biomedical Research and Research Training	000	3	7/20/2022	NON-COMPETING CONTINUATION	$302,504
														Subtotal = $302,504

Issue Date FY: 2021 ( Subtotal = $302,504 )
2021	2021	GEORGIA TECH RESEARCH CORPORATION	926 DALNEY ST NW	ATLANTA	GA	30332	FULTON	USA	Biomedical Research and Research Training	000	2	6/28/2021	NON-COMPETING CONTINUATION	$302,504
														Subtotal = $302,504

Issue Date FY: 2020 ( Subtotal = $302,422 )
2020	2020	GEORGIA TECH RESEARCH CORPORATION	926 DALNEY ST NW	ATLANTA	GA	30318	FULTON	USA	Biomedical Research and Research Training	001	1	9/4/2020	NEW	$717
2020	2020	GEORGIA TECH RESEARCH CORPORATION	926 DALNEY ST NW	ATLANTA	GA	30318	FULTON	USA	Biomedical Research and Research Training	000	1	9/2/2020	NEW	$301,705
														Subtotal = $302,422

Grand Total All Awards = $1,638,968

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Development of a Rapid Antibiotic Susceptibility Test Capable of Detecting Heteroresistance

Award Number: R35GM138354

ORGANIZATION: NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/15/2020

PERIOD OF PERFORMANCE END DATE: 06/30/2026

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