C25-modified rifamycin derivatives with improved activity against Mycobacterium abscessus.

ABSTRACT: Infections caused by Mycobacterium abscessus are difficult to treat due to its intrinsic resistance to most antibiotics. Formation of biofilms and the capacity of M. abscessus to survive inside host phagocytes further complicate eradication. Herein, we explored whether addition of a carbamate-linked group at the C25 position of rifamycin SV blocks enzymatic inactivation by Arr_Mab, an ADP-ribosyltransferase conferring resistance to rifampicin (RMP). Unlike RMP, 5j, a benzyl piperidine rifamycin derivative with a morpholino substituted C3 position and a naphthoquinone core, is not modified by purified Arr_Mab. Additionally, we show that the Arr_Mab D82 residue is essential for catalytic activity. Thermal profiling of Arr_Mab in the prese

SUBMITTER: Paulowski L 

PROVIDER: S-EPMC9802118 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature