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Reinforcing the barrier: Understanding how cell envelope modifications promote intrinsic antimicrobial tolerance and resistance in Acinetobacter baumannii

Award Number: R35GM143053
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: 07/01/2021
PERIOD OF PERFORMANCE END DATE: 04/30/2026

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Reinforcing the barrier: Understanding how cell envelope modifications promote intrinsic antimicrobial tolerance and resistance in Acinetobacter baumannii - Project Summary/Abstract Emergence of multidrug and extensively drug resistant Gram-negative bacteria is a growing problem that threatens established antimicrobial treatment protocols. Acinetobacter baumannii is an emerging critical threat pathogen notorious for its ability to rapidly develop intrinsic multidrug resistance. A. baumannii causes hospital-acquired infections, which manifest as bacteremia, urinary tract and wound infections. In the US, an estimated 60% of hospital-acquired A. baumannii infections were multidrug resistant, often including carbapenem resistance, which leaves colistin as the “last-resort” treatment option. However, colistin resistance has also emerged. There is an urgent need to understand intrinsic mechanisms that promote antibiotic resistance phenotypes in A. baumannii to guide alternative antimicrobial strategies. Our preliminary work has identified factors that promote acquisition of multidrug resistance, including carbapenem and colistin resistance, in A. baumannii. Specifically, links between the outer membrane and peptidoglycan layers of the cell envelope are key for the resistance phenotypes, where one layer compensates for defects in the other. While enzymes that assemble the outer membrane and cell wall are largely known, A. baumannii encodes unique regulatory mechanisms to control their activity in response to stress. In this proposal, we will address three important questions to understand intrinsic antibiotic resistance in A. baumannii. The questions will explore the relationship between peptidoglycan and outer membrane assembly, which is poorly understood in Gram-negative bacteria. Findings from this work will enable us to build a model of intrinsic factors in A. baumannii that lead to multidrug resistance and will help in the design of combinatorial drug regimens that target both essential layers, thus precluding resistance; consequently, our findings support the National Institute of Health mission, which aims to foster fundamental discoveries to reduce human disease.


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 = $390,000 )
2025	2025	UNIVERSITY OF TEXAS AT DALLAS	800 WEST CAMPBELL RD.	RICHARDSON	TX	75080	DALLAS	USA	Biomedical Research and Research Training	003	6	4/7/2025	NON-COMPETING CONTINUATION	$390,000
2025	2023	UNIVERSITY OF TEXAS AT DALLAS	800 WEST CAMPBELL RD.	RICHARDSON	TX	75080	DALLAS	USA	Biomedical Research and Research Training	002	4	12/18/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$49,376
2025	2023	UNIVERSITY OF TEXAS AT ARLINGTON	701 S NEDDERMAN DR	ARLINGTON	TX	76019	TARRANT	USA	Biomedical Research and Research Training	001	3	12/18/2024	NON-COMPETING CONTINUATION	-$1
2025	2022	UNIVERSITY OF TEXAS AT ARLINGTON	701 S NEDDERMAN DR	ARLINGTON	TX	76019	TARRANT	USA	Biomedical Research and Research Training	000	2	12/18/2024	NON-COMPETING CONTINUATION	-$49,375
														Subtotal = $390,000

Issue Date FY: 2024 ( Subtotal = $390,000 )
2024	2024	UNIVERSITY OF TEXAS AT DALLAS	800 WEST CAMPBELL RD.	RICHARDSON	TX	75080	DALLAS	USA	Biomedical Research and Research Training	001	5	7/30/2024	NON-COMPETING CONTINUATION	$39,000
2024	2024	UNIVERSITY OF TEXAS AT DALLAS	800 WEST CAMPBELL RD.	RICHARDSON	TX	75080	DALLAS	USA	Biomedical Research and Research Training	000	5	3/27/2024	NON-COMPETING CONTINUATION	$351,000
														Subtotal = $390,000

Issue Date FY: 2023 ( Subtotal = $389,999 )
2023	2023	THE UNIVERSITY OF TEXAS AT ARLINGTON	701 S. NEDDERMAN DR	ARLINGTON	TX	76019	TARRANT	USA	Biomedical Research and Research Training	000	3	4/4/2023	NON-COMPETING CONTINUATION	$366,610
2023	2023	UNIVERSITY OF TEXAS AT DALLAS	800 WEST CAMPBELL RD.	RICHARDSON	TX	75080	DALLAS	USA	Biomedical Research and Research Training	002	4	8/1/2023	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$389,998
2023	2023	THE UNIVERSITY OF TEXAS AT ARLINGTON	701 S. NEDDERMAN DR	ARLINGTON	TX	76019	TARRANT	USA	Biomedical Research and Research Training	001	3	7/31/2023	NON-COMPETING CONTINUATION	-$366,609
														Subtotal = $389,999

Issue Date FY: 2022 ( Subtotal = $366,610 )
2022	2022	UNIVERSITY OF TEXAS AT ARLINGTON	400 S CORN ST	ARLINGTON	TX	76019	TARRANT	USA	Biomedical Research and Research Training	000	2	4/7/2022	NON-COMPETING CONTINUATION	$329,948
2022	2022	THE UNIVERSITY OF TEXAS AT ARLINGTON	701 S. NEDDERMAN DR	ARLINGTON	TX	76019	TARRANT	USA	Biomedical Research and Research Training	001	2	7/13/2022	NON-COMPETING CONTINUATION	$36,662
														Subtotal = $366,610

Issue Date FY: 2021 ( Subtotal = $366,610 )
2021	2021	UNIVERSITY OF TEXAS AT ARLINGTON	400 S CORN ST	ARLINGTON	TX	76019	TARRANT	USA	Biomedical Research and Research Training	000	1	6/23/2021	NEW	$366,610
														Subtotal = $366,610

Grand Total All Awards = $1,903,219

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Reinforcing the barrier: Understanding how cell envelope modifications promote intrinsic antimicrobial tolerance and resistance in Acinetobacter baumannii

Award Number: R35GM143053

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: 07/01/2021

PERIOD OF PERFORMANCE END DATE: 04/30/2026

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