Novel targets and inhibitors of the Mycobacterium tuberculosis cytochrome bd oxidase to foster anti-tuberculosis drug discovery.

A deeper structure-mechanistic understanding of Mtb's cyt- is a prerequisite for efforts to: (i) identify pathogen specific targets for the design of novel nontoxic hit molecules, forming the platform for the development of new leads, (ii) design mechanism of action studies, (iii) perform medicinal chemistry of existing inhibitors to improve their potency and pharmacokinetic/-dynamic properties. Phase studies with such optimized cyt- inhibitors in combination with anti-TB compounds targeting the oxidative phosphorylation pathway is recommended.