Mycobacteria Cell Wall

Background: Benzothiazinones inhibit cell wall arabinan biosynthesis, which is lethal for Corynebacterineae. Results: Corynebacteria can evade the action of benzothiazinones in the absence of decaprenyl phosphoribose synthesis by increasing the intracellular decaprenyl phosphate pool. Conclusion: Benzothiazinones induce synthetic lethality in Corynebacterineae by blocking decaprenyl phosphate recycling. Significance: Increased production of decaprenyl phosphate is a new mechanism of resistance to benzothiazinones.

Background: The development of new drugs against tuberculosis and diphtheria is focused on disrupting the biogenesis of the cell wall, the unique architecture of which confers resistance against current therapies. The enzymatic pathways involved in the synthesis of the cell wall by these pathogens are well understood, but the underlying regulatory mechanisms are largely unknown.