Mycothione reductase as a potential target in the fight against Mycobacterium abscessus infections

While infections caused by Mycobacterium abscessus complex (MABC) are rising worldwide, the current treatment of these infections is far from ideal due to its numerous shortcomings thereby increasing the urge for novel drug targets. In this study, mycothione reductase (Mtr) was evaluated for its potential as a drug target for 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. First, a Mab increment mtr mutant strain was generated, lacking mtr expression. Next, the in vitro sensitivity of Mab increment mtr to oxidative stress and antimycobacterial drugs was determined. Finally, we evaluated the intramacrophage survival and the virulence of Mab increment mtr in Galleria mellonella larvae. Mab increment mtr demonstrated a 39.5-fold reduction in IC90 when exposed to bedaquiline in vitro. Furthermore, the Mab increment mtr mutant showed a decreased ability to proliferate inside macrophages and larvae, suggesting that Mtr plays an important role during MABC infection. Altogether, these findings support the assumption of Mtr being a potential target for antimycobacterial drugs.