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NOBEL PRIZE 2026

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NIHNATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

Regulation of antibiotic tolerance in Mycobacterium abscessus by proteolytic signaling

Completed
Institution
UNIVERSITY OF CALIFORNIA AT DAVIS, CA
Principal investigator
Bennett Penn
Funding
$201K
Duration
2024–2026
Open portfolio

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Abstract

ABSTRACT: Nontuberculous mycobacteria (NTM) infections such as Mycobacterium abscessus (Mabs) are a growing health concern, particularly in older and immunocompromised patient populations, and are among the most difficult bacterial infections to eradicate. Thus, there remains a critical need to understand the mechanisms enabling Mabs to survive prolonged exposure to lethal antibiotics. The central hypothesis of this proposal is that antibiotic tolerance is a regulated process, controlled by pathways that sense discrete stresses, and transduce signals leading to a coordinated cellular response that mitigates antibiotic cytotoxicity. In our preliminary data we present the results of a Tn-Seq screen to identify genes contributing to antibiotic tolerance. We now propose to use cutting-edge proteomics to study several proteases that were identified in the Tn-Seq screen.

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NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASESR21Anti-Infective Resistance and Targets Study Section [AIRT]tolerancemycobacteriaantibioticmycobacteriumscreenscreen identifymabsntm

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