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The Role of Atypical Cell Wall Biology of Mycobacterium abscessus in Pulmonary Infection and Therapy

Award Number: F31HL147392
ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 03/19/2019
PERIOD OF PERFORMANCE END DATE: 11/02/2020

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The Role of Atypical Cell Wall Biology of Mycobacterium abscessus in Pulmonary Infection and Therapy - PROJECT SUMMARY Patients with structural lung conditions, such as cystic fibrosis and bronchiectasis are highly susceptible to infections with Mycobacterium abscessus. These pathogens are detected in the sputum of ~13% of cystic fibrosis patients in the US. In addition to those with underlying lung conditions, immune competent post-menopausal Caucasian women are also selectively susceptible to pulmonary M. abscessus infections. Despite increasing prevalence of this disease, very little is known about the pathogenesis of pulmonary infections with M. abscessus. This proposal’s aim is to fill critical gaps in our understanding of pulmonary M. abscessus infection. Recent studies have demonstrated that the peptidoglycan, the exoskeleton of the bacterial cell, of M. abscessus is unique in the final step of its synthesis compared to other gram negative and gram positive bacteria. Furthermore, this distinction is due to the activities of non-classical transpeptidases. I will study the relevance of these novel transpeptidases to the physiology of M. abscessus peptidoglycan and their contribution during acute and chronic stages of pulmonary infection. Investigating M. abscessus in vivo is critical, however current published accounts of mouse models often lack a sustained chronic infection analogous to what would occur in cystic fibrosis or bronchiectasis patients. They also lack demonstrated progression to pathology. I have developed a mouse model which fulfills both of these criteria, generating not only a chronic M. abscessus pulmonary infection, but also leading to gross pathological findings that mimic those observed in humans. The studies outlined in this proposal will provide new insights into aspects of M. abscessus cell wall metabolism and physiology during infection that could lead to novel therapeutic development and novel chemotherapy regimens of existing antibiotics.


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: 2022 ( Subtotal = -$567 )
2022	2020	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Lung Diseases Research	001	2	4/22/2022	NON-COMPETING CONTINUATION	-$567
2022	2019	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Lung Diseases Research	000	1	4/22/2022	NEW	$0
														Subtotal = -$567

Issue Date FY: 2021 ( Subtotal = -$28,429 )
2021	2020	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Lung Diseases Research	000	2	6/24/2021	NON-COMPETING CONTINUATION	-$28,429
														Subtotal = -$28,429

Issue Date FY: 2020 ( Subtotal = $45,520 )
2020	2020	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Lung Diseases Research	000	2	3/10/2020	NON-COMPETING CONTINUATION	$45,520
														Subtotal = $45,520

Issue Date FY: 2019 ( Subtotal = $45,016 )
2019	2019	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Lung Diseases Research	001	1	3/19/2019	NEW	$0
2019	2019	JOHNS HOPKINS UNIVERSITY, THE	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Lung Diseases Research	000	1	3/19/2019	NEW	$45,016
														Subtotal = $45,016

Grand Total All Awards = $61,540

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The Role of Atypical Cell Wall Biology of Mycobacterium abscessus in Pulmonary Infection and Therapy

Award Number: F31HL147392

ORGANIZATION: NATIONAL HEART, LUNG, & BLOOD INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 03/19/2019

PERIOD OF PERFORMANCE END DATE: 11/02/2020

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