Mycobacterium avium subspecies paratuberculosis cell membrane and associated redox targets

The Mycobacterium avium subspecies paratuberculosis (MAP) cell membrane and associated redox targets comprise the structural and metabolic components of the MAP cell envelope and its respiratory system (RedHill Biopharma, 2024). This target is primarily associated with the mechanism of action of clofazimine, a riminophenazine antibiotic used in the treatment of mycobacterial infections, including those linked to Crohn's disease (Expert Opinion on Biological Therapy, 2019). Specifically, clofazimine interacts with membrane-bound enzymes such as NADH dehydrogenase 2 (NDH-2), which is the primary respiratory chain oxidoreductase in mycobacteria (ResearchGate, 2018). Through a process of enzymatic reduction and subsequent non-enzymatic oxidation, known as redox cycling, clofazimine generates lethal levels of reactive oxygen species (ROS) like superoxide and hydrogen peroxide (NIH, 2016). This oxidative stress disrupts the bacterial cell membrane, inhibits energy production, and ultimately leads to the death of the pathogen (Frontiers in Microbiology, 2012). Targeting these redox pathways is a key therapeutic strategy for eradicating persistent MAP, which is implicated in chronic granulomatous enteritis in both animals and humans (MDPI, 2023).

Other names

MAP cell membrane and associated redox targetsNADH dehydrogenase 2 (NDH-2)Type II NADH:quinone oxidoreductaseMycobacterial respiratory chainMAP cell membrane

Redox cycling via NADH dehydrogenase 2 (NDH-2) leading to reactive oxygen species (ROS) production and membrane disruption