ABSTRACT
Intracellular pathogens are able to counteract the oxidative stress response generated by the host cells (Lamichhane, 2011; Nambi et al., 2015; Pai et al., 2016). In this oxidative stress interplay, macrophages exert the first response reaction to the bacterial infection, generating reactive oxygen (ROS) and reactive nitrogen species (RNS) to kill the pathogen (Lamichhane, 2011). In Actinomycetes, exogenous oxidative stresses are counteracted by the mycothiol (MSH; 1-d-myo-inosityl 2-(N-acetylcysteinyl)amido-2-deoxy-α-d-glucopyranoside) system, which is analogous to the well-studied glutathione (GSH) system (Fahey, 2013; Van Laer et al., 2013; Reyes et al., 2018). MSH is a unique cysteinyl pseudodisaccharide that is responsible for the tight control of the redox environment in mycobacteria and is a key molecule that protects against the irreversible harm generated by ROS and RNS and that rescues sulfur-containing molecules from permanent damage and subsequent inactivation and/or degradation. Gram-negative bacteria and most eukaryotes rely on GSH as the main low-molecular-weight (LMW) thiol to maintain the redox homeostasis. However, Actinomycetes, such as Mycobacterium tuberculosis, depend greatly on MSH, hence, conferring a crucial role to this intracellular redox system (Newton et al., 2008). In this chapter, MSH and its molecular partners will be presented, providing a general perspective on its protective mechanism and pathways.
