Therapeutic efficacy of antimalarial drugs targeting DosRS signaling in Mycobacterium abscessus.

ABSTRACT: A search for alternative Mycobacterium abscessus treatments led to our interest in the two-component regulator DosRS, which, in Mycobacterium tuberculosis, is required for the bacterium to establish a state of nonreplicating, drug-tolerant persistence in response to a variety of host stresses. We show here that the genetic disruption of dosRS impairs the adaptation of M. abscessus to hypoxia, resulting in decreased bacterial survival after oxygen depletion, reduced tolerance to a number of antibiotics in vitro and in vivo, and the inhibition of biofilm formation. We determined that three antimalarial drugs or drug candidates, artemisinin, OZ277, and OZ439, can target DosS-mediated hypoxic signaling in M. abscessus and recapitulate the phenotypic effects o

SUBMITTER: Belardinelli JM 

PROVIDER: S-EPMC8943825 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature