top of page


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

L De Vooght(1) T Piller(1) L Van Moll(1) P Cos(1)

1:University of Antwerp

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 Mabmtr mutant strain was generated, lacking mtr expression. First, the in vitro sensitivity of Mabmtr to oxidative stress and antimycobacterial drugs was determined. Next, we evaluated the intramacrophage survival and the virulence of Mabmtr in Galleria mellonella larvae. We showed that abrogation of mtr expression sensitizes the Mabmtr mutant to oxidative stress and antimycobacterial drugs. Mabmtr demonstrated a 39.5-fold reduction in IC90 when exposed to bedaquiline in vitro. Finally, the Mabmtr 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.

bottom of page