Understanding the physiological role of cofactor F 420 in mycobacterium

Abstract

The unique deazaflavin cofactor F420 occurs widely among mycobacterial species, including pathogenic ones. It is also involved in the activation of the antitubercular prodrug PA-824. We created a KO-mutant of F420 in M. bovis BCG to study the physiological significance of this cofactor in mycobacteria. Using nitric oxide sensitivity and hypoxia models, both immensely relevant in tuberculosis research, we discovered that the F420 KO-mutants were very highly susceptible to death by nitrosative stress and unable to rejuvenate as robustly as wild type BCG after exposure to hypoxic conditions. Due to time constraints, we could not proceed with molecular anaylsis of the mechanisms underlying our findings. Nevertheless, this opens new avenues for antitubercular drug discovery with basis on cofactor biochemistry.