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The PDIM paradox of M. tuberculosis

Award Number: R01AI175972
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: 02/01/2023
PERIOD OF PERFORMANCE END DATE: 01/31/2028

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The PDIM paradox of M. tuberculosis - Project Summary Mycobacterium tuberculosis (Mtb) has been the leading cause of infectious disease mortality worldwide for the past few decades with more than 1 million deaths annually. This pathogen has an exceptionally complex cell wall structure, the outer components of which are important for direct interactions with the host, for giving structural support and maintaining a hydrophobic barrier for small molecules and antibiotics. Phthiocerol dimycocerosate (PDIM) is a lipid found in the outer-most layer of the Mtb cell envelope. PDIMs form a permeability barrier, protecting the bacteria from antimicrobial compounds, and are important virulence factors for defense against the host immune system. Paradoxically, despite these important functions, PDIM is dispensable in vitro and its loss confers a growth advantage leading to the selection of spontaneously occurring PDIM negative clones in laboratory cultures. This affects experimental reliability, reproducibly and the interpretation of results. PDIM loss leads to reduced cell wall permeability and virulence attenuation, producing misleading results in infection experiments, drug susceptibility testing and genetic manipulations. To remove PDIM bias from TB research, and to study PDIMs role in pathogenesis and drug tolerance, we need appropriate screening and selection tools. In this grant application we will build on powerful new preliminary results to develop robust PDIM selection, screening and cleanup protocols, determine the propensity of PDIM loss in different Mtb strains and its impact on virulence, and aim to study how PDIM population heterogeneity and propionate metabolism impact infectivity and antibiotic persistence.


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: 2026 ( Subtotal = $501,801 )
2026	2026	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Allergy and Infectious Diseases Research	000	4	12/31/2025	NON-COMPETING CONTINUATION	$501,801
														Subtotal = $501,801

Issue Date FY: 2025 ( Subtotal = $501,801 )
2025	2025	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Allergy and Infectious Diseases Research	000	3	1/7/2025	NON-COMPETING CONTINUATION	$501,801
														Subtotal = $501,801

Issue Date FY: 2024 ( Subtotal = $501,801 )
2024	2024	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Allergy and Infectious Diseases Research	000	2	1/23/2024	NON-COMPETING CONTINUATION	$451,621
2024	2024	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Allergy and Infectious Diseases Research	001	2	5/28/2024	NON-COMPETING CONTINUATION	$50,180
														Subtotal = $501,801

Issue Date FY: 2023 ( Subtotal = $501,801 )
2023	2023	ALBERT EINSTEIN COLLEGE OF MEDICINE	1300 MORRIS PARK AVE	BRONX	NY	10461	BRONX	USA	Allergy and Infectious Diseases Research	000	1	1/26/2023	NEW	$501,801
														Subtotal = $501,801

Grand Total All Awards = $2,007,204

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The PDIM paradox of M. tuberculosis

Award Number: R01AI175972

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: 02/01/2023

PERIOD OF PERFORMANCE END DATE: 01/31/2028

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