Sunday, July 6, 2025 7/6/2025

Origins of zinc starvation in Mycobacterium tuberculosis during chronic infection

Award Number: R21AI163599
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/08/2021
PERIOD OF PERFORMANCE END DATE: 05/31/2025

Group Awards By:

View Award Description

Origins of zinc starvation in Mycobacterium tuberculosis during chronic infection - Summary Tuberculosis (TB) is a major public health burden in the world: over a million people die of the disease every year and an estimated one third of the world’s population harbor the pathogen Mycobacterium tuberculosis (Mtb). Treatment of TB requires 6 to 9 months of an antibiotic regimen comprising of multiple antibiotics. Difficulties in treatment of TB are largely attributed to non-inheritable drug resistance in the pathogen that are considered to be developed due to unique microenvironments in the host (e.g. nutrient depletion, hypoxia and antibiotic exposure). Recently, we uncovered one such condition: zinc starvation. In response to zinc starvation both Mycobacterium smegmatis and Mycobacterium tuberculosis induce ribosome remodeling and ribosome hibernation. Ribosome remodeling involves replacement of multiple ribosomal (r-) proteins containing the zinc-binding CXXC motif (therefore called C+ r-proteins) by their motif- free C- paralogues. Ribosome hibernation involves binding of mycobacterial protein Y (Mpy) to the decoding center of the C- ribosome. Ribosome remodeling occurs at a zinc concentration that permits growth, whereas ribosome hibernation occurs at a growth-restrictive concentration of zinc. Moreover, mycobacterial cells harboring remodeled and hibernating ribosomes are resistant to aminoglycosides and spectinamides. Furthermore, we demonstrated that zinc in the host lung environment during chronic Mtb infection is low enough to induce ribosome remodeling and Mpy- dependent resistance to streptomycin, an aminoglycoside used in the treatment of multi-drug resistant TB. However, the underlying cause for zinc starvation in Mtb during chronic infection is not known. Based on the idea that metal ion starvation during bacterial infections is an innate host defense strategy, called nutritional immunity, we propose to identify the components of host immune system responsible for zinc starvation in Mtb (Aim 1), and determine the potential of zinc oxide nanoparticles as an adjunct therapeutic (Aim 2). Upon completion of the project we will gain further insight into the cause of zinc starvation and related ribosome remodeling/hibernation in Mtb during chronic infection, and develop a therapeutic strategy to minimize the drug resistance caused by these changes to the ribosome in Mtb.


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: 2024 ( Subtotal = $0 )
2024	2022	HEALTH RESEARCH, INC.	150 BROADWAY STE 280	MENANDS	NY	12204	ALBANY	USA	Allergy and Infectious Diseases Research	000	2	4/3/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $201,128 )
2022	2022	HEALTH RESEARCH, INC.	EMPIRE STATE PLAZA	ALBANY	NY	12237	ALBANY	USA	Allergy and Infectious Diseases Research	000	2	6/2/2022	NON-COMPETING CONTINUATION	$201,128
														Subtotal = $201,128

Issue Date FY: 2021 ( Subtotal = $223,662 )
2021	2021	HEALTH RESEARCH, INC.	EMPIRE STATE PLAZA	ALBANY	NY	12237	ALBANY	USA	Allergy and Infectious Diseases Research	000	1	6/9/2021	NEW	$223,662
														Subtotal = $223,662

Grand Total All Awards = $424,790

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Origins of zinc starvation in Mycobacterium tuberculosis during chronic infection

Award Number: R21AI163599

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 06/08/2021

PERIOD OF PERFORMANCE END DATE: 05/31/2025

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer