Blocking Bacterial Naphthohydroquinone Oxidation and ADP-Ribosylation Improves Activity of Rifamycins against Mycobacterium abscessus.

ABSTRACT: Rifampicin is an effective drug for treating tuberculosis (TB) but is not used to treat Mycobacterium abscessus infections due to poor in vitro activity. While rifabutin, another rifamycin, has better anti-M. abscessus activity, its activity is far from the nanomolar potencies of rifamycins against Mycobacterium tuberculosis. Here, we asked (i) why is rifabutin more active against M. abscessus than rifampicin, and (ii) why is rifabutin's anti-M. abscessus activity poorer than its anti-TB activity? Comparative analysis of naphthoquinone- versus naphthohydroquinone-containing rifamycins suggested that the improved activity of rifabutin over rifampicin is linked to its less readily oxidizable naphthoquinone core. Although rifabutin is resistant to bacterial oxidation, metabolite and ge

SUBMITTER: Ganapathy US 

PROVIDER: S-EPMC8370238 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature