Auranofin activity exposes thioredoxin reductase as a viable drug target in Mycobacterium abscessus.

Auranofin activity exposes thioredoxin reductase as a viable drug target in Mycobacterium abscessus. Antimicrob Agents Chemother. 2019 Jul 01;: Authors: Ruth MM, van Rossum M, Koeken VACM, Pennings L, Svensson EM, Ruessen C, Bowles EC, Wertheim HFL, Hoefsloot W, van Ingen J Abstract Non-tuberculous mycobacteria (NTM) are highly drug-resistant, opportunistic pathogens that can cause pulmonary disease. Outcomes of currently recommended treatment regimens are poor, especially for M. abscessus New or repurposed drugs are direly needed. Auranofin, a gold-based antirheumatic agent, was investigated for M. tuberculosis. Here, we test auranofin against NTM, in vitro and ex vivoWe tested the susceptibility of 63 NTM isolates to auranofin using broth microdilution. Next, we assessed synergy between auranofin and antimycobacterial drugs using the checkerboard method and calculated the fractional inhibition concentration index (FICI). Using time-kill kinetics assays (TK), we assessed pharmacodynamics of auranofin alone and in combination with drug combinations showing the lowest FICIs for M. abscessus CIP 104536. A response surface analysis was used to assess synergistic interactions over time in TKs. Primary isolated macrophages were infected with M. abscessus and treated with auranofin. Finally, using KEGG Orthology, we looked for orthologues to auranofins drug target in M. tuberculosis. M. abscessus had the lowest MIC50 on auranofin among tes...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research