P044

While infections caused by Mycobacterium abscessus complex (MABC) are rising worldwide, the current treatment of these infections delivers unsatisfactory cure rates despite long-term use of multidrug regimens. Absence of an optimal treatment regimen and the emergence of multi-drug resistance in clinical isolates necessitates the need for the discovery of better/new drugs to combat these infections. In this study, mycothione reductase (Mtr) was evaluated for its potential as a novel drug target to treat MABC infections since it is a key enzyme needed in the recycling of mycothiol, the main low-molecular-weight thiol protecting the bacteria against reactive oxygen species and other reactive intermediates. For this, a Mab∆mtr mutant strain was generated, lacking mtr expression. First, the in vitro sensitivity of Mab∆mtr to oxidative stress and antimycobacterial drugs was determined. Next, we evaluated the intramacrophage survival and the virulence of Mab∆mtr in Galleria mellonella larvae. We showed that abrogation of mtr expression sensitizes the Mab∆mtr mutant to oxidative stress and antimycobacterial drugs. Mab∆mtr demonstrated a 39.5-fold reduction in IC90 when exposed to bedaquiline in vitro. Finally, the Mab∆mtr mutant showed a decreased ability to proliferate inside macrophages and larvae, suggesting that Mtr plays an important role during MABC infection and thus making it a potential target for drug discovery.