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Characterization of the nutrient assimilation pathways in M. tuberculosis

Award Number: R01AI150916
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: 11/19/2020
PERIOD OF PERFORMANCE END DATE: 10/31/2025

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Characterization of the nutrient assimilation pathways in M. tuberculosis - Project Summary / Abstract Mtb utilizes host-derived lipids to promote pathogenesis and this is a defining feature of this intracellular pathogen. During infection Mtb imports and metabolizes host lipids to support pathogenesis by producing: i) energy, ii) central metabolic intermediates, or iii) polyketide virulence lipids. While the metabolic pathways in Mtb that degrade or process lipids are complex and contain redundant enzymes, the bacterial Mce lipid transporters appear to be specific for dedicated lipid substrates. Aim 1 of this work proposes to employ genetic and biochemical approaches to identify and characterize novel gene/proteins required for fatty acid import in Mtb. While it is understood that Mce1 imports fatty acids, the substrate specificity of this transporter is unknown. Therefore, we intend to define substrates and the biochemical basis of Mce1 substrate specificity. Our preliminary studies indicate that Mtb transports fatty acid precursors of immune signaling lipids via Mce1 and we include here studies to evaluate if scavenging of this immune lipid precursors by Mtb impacts the immune response. Aim 2 proposes to identify and characterize protein subunits that are shared by all the Mce transporters and are required for lipid import in Mtb. We have determined that LucA is required for Mce1- and Mce4-mediated transport and LucA stabilizes these transporter complexes. These studies seek to characterize the basis for this transporter stabilization. Similarly, MceG is required for Mce1- and Mce4-mediated transport and we intend to understand how MceG stabilizes and interacts with Mce1. We will use a genetic approach to silence LucA and MceG in Mtb within chronically infected mice and quantify bacterial fitness to determine the therapeutic potential of drugs that potentially block these proteins.


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 = $527,826 )
2025	2025	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Allergy and Infectious Diseases Research	000	5	10/30/2024	NON-COMPETING CONTINUATION	$527,826
														Subtotal = $527,826

Issue Date FY: 2024 ( Subtotal = $598,288 )
2024	2024	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Allergy and Infectious Diseases Research	001	4	5/15/2024	NON-COMPETING CONTINUATION	$59,829
2024	2024	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Allergy and Infectious Diseases Research	000	4	10/25/2023	NON-COMPETING CONTINUATION	$538,459
														Subtotal = $598,288

Issue Date FY: 2023 ( Subtotal = $598,288 )
2023	2023	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Allergy and Infectious Diseases Research	000	3	10/26/2022	NON-COMPETING CONTINUATION	$598,288
														Subtotal = $598,288

Issue Date FY: 2022 ( Subtotal = $640,202 )
2022	2022	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Allergy and Infectious Diseases Research	000	2	10/13/2021	NON-COMPETING CONTINUATION	$640,202
														Subtotal = $640,202

Issue Date FY: 2021 ( Subtotal = $571,814 )
2021	2021	CORNELL UNIVERSITY	341 PINE TREE RD	ITHACA	NY	14850	TOMPKINS	USA	Allergy and Infectious Diseases Research	000	1	11/18/2020	NEW	$571,814
														Subtotal = $571,814

Grand Total All Awards = $2,936,418

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Characterization of the nutrient assimilation pathways in M. tuberculosis

Award Number: R01AI150916

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: 11/19/2020

PERIOD OF PERFORMANCE END DATE: 10/31/2025

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