While target-based
drug design has proved successful in several therapeutic areas, this approach has not yet provided compelling outcomes in the field of
antibacterial agents. This statement remains especially true for the development of novel therapeutic interventions against
tuberculosis, an
infectious disease that is among the top ten leading causes of death globally. Mycobacterial
galactan is an important component of the protective cell wall core of the
tuberculosis pathogen and it could provide a promising target for the design of new drugs. In this review, we summarize the current knowledge on
galactan biosynthesis in Mycobacterium tuberculosis, including landmark findings that led to the discovery and understanding of three key
enzymes in this pathway:
UDP-galactose mutase, and galactofuranosyl
transferases GlfT1 and GlfT2. Moreover, we recapitulate the efforts aimed at their inhibition. The predicted common transition states of the three
enzymes provide the lucrative possibility of multitargeting in
pharmaceutical development, a favourable property in the mitigation of drug resistance. We believe that a tight interplay between target-based computational approaches and experimental methods will result in the development of original inhibitors that could serve as the basis of a new generation of drugs against
tuberculosis.