Wednesday, January 15, 2025 1/15/2025

Discovery and characterization of new bacterial cell wall targets and inhibitors to treat resistant infections

Award Number: R01AI148752
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By:

View Award Abstract

Project Summary Antibiotic-resistant bacterial infections pose a substantial and growing threat to human health. There is a pressing need to characterize new antibacterial targets and to develop methods that enable discovery and characterization of inhibitors for these targets. The research described here focuses on understanding late steps in the assembly of the peptidoglycan cell wall that surrounds bacterial cells. The cell wall is essential for bacterial survival, making it an outstanding target for antibiotics. Indeed, some of the most important antibiotics in history, the beta-lactams and the glycopeptides, target late steps in peptidoglycan assembly. Historically, the enzymes that catalyze these late steps have been extremely difficult to study due to the nature of the substrates that are required, the products that are formed, and the fact that many peptidoglycan biosynthetic enzymes are polytopic membrane proteins or function only when complexed to a membrane protein. Recent technological innovations made in our labs have advanced the field of peptidoglycan biosynthesis considerably, and we are able to pursue challenging targets that have not previously been studied. This project has four aims. Aim 1 involves further development of chemical tools to enable mechanistic and structural studies of cell wall biosynthetic enzymes. Aim 2 focuses on understanding MurJ, the flippase that exports the peptidoglycan precursor Lipid II from the cytoplasm to the cell surface where it is polymerized to produce peptidoglycan. Aim 3 focuses on characterizing FtsW, the only universally conserved peptidoglycan polymerase in bacteria. Aim 4 focuses on two novel Staphylococcus aureus cell wall hydrolase complexes that process uncrosslinked peptidoglycan before it is integrated into the cell wall. These four aims will provide fundamental information on how the bacterial cell wall is built. The studies will also provide new chemical tools, assays, and scientific knowledge to enable the discovery of inhibitors that may be useful for treating resistant bacterial infections.


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 = $801,392 )
2025	2025	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	6	12/9/2024	COMPETING CONTINUATION	$801,392
														Subtotal = $801,392

Issue Date FY: 2024 ( Subtotal = $767,231 )
2024	2024	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	5	12/19/2023	NON-COMPETING CONTINUATION	$690,507
2024	2024	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	001	5	5/21/2024	NON-COMPETING CONTINUATION	$76,724
														Subtotal = $767,231

Issue Date FY: 2023 ( Subtotal = $767,231 )
2023	2023	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	4	12/9/2022	NON-COMPETING CONTINUATION	$767,231
														Subtotal = $767,231

Issue Date FY: 2022 ( Subtotal = $767,231 )
2022	2022	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	3	12/16/2021	NON-COMPETING CONTINUATION	$767,231
														Subtotal = $767,231

Issue Date FY: 2021 ( Subtotal = $767,231 )
2021	2021	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	2	12/30/2020	NON-COMPETING CONTINUATION	$767,231
														Subtotal = $767,231

Issue Date FY: 2020 ( Subtotal = $767,231 )
2020	2020	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	001	1	1/7/2020	NEW	$0
2020	2020	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	000	1	12/30/2019	NEW	$767,231
2020	2020	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Allergy and Infectious Diseases Research	002	1	8/24/2020	NEW	$0
														Subtotal = $767,231

Grand Total All Awards = $4,637,547

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Discovery and characterization of new bacterial cell wall targets and inhibitors to treat resistant infections

Award Number: R01AI148752

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer