α-Glucan pathway as a novel Mtb drug target: structural insights and cues for polypharmcological targeting of GlgB and GlgE.

Tuberculosis continues to be a deadly infectious disease, mainly due to the existence of persistent bacterial populations that survive drug treatment and obstruct complete eradication of infection. The enzymes GlgE and GlgB, which are involved in the glycan pathway, have recently been identified as promising drug targets for combating persistent bacillus strains. In the glycan pathway, enzymes GlgE, GlgA, and Tre-xyz produce linear α-glucans, which are then converted to essential branched α-glucan by GlgB. This α-glucan is a vital cell-wall and storage polysaccharide, critical for Mtb virulence and persistence. We highlight recent insights into the significance of both GlgE and GlgB in the glycan pathway and also discuss drug strategies for tuberculosis such as polypharmcological targeting of GlgB and GlgE. Small molecule-based modulation of GlgB and GlgE to boost the design and development of novel and improved drugs for more selective and efficient targeting of tuberculosis are also discussed.