Mannopyranoside Glycolipids Inhibit Mycobacterial and Biofilm Growth and Potentiate Isoniazid Inhibition Activities in M. smegmatis

Abstract

Lipomannan and lipoarabinomannan are integral components of the mycobacterial cell wall. Earlier studies demonstrated that synthetic arabinan and arabinomannan glycolipids acted as inhibitors of mycobacterial growth, in addition to exhibiting inhibitory activities of mycobacterial biofilm. Herein, it is demonstrated that synthetic mannan glycolipids are better inhibitors of mycobacterial growth, whereas lipoarabinomannan has a higher inhibition efficiency to biofilm. Syntheses of mannan glycolipids with a graded number of mannan moieties and an arabinomannan glycolipid are conducted by chemical methods and subsequent mycobacterial growth and biofilm inhibition studies are conducted on Mycobacterium smegmatis. Growth inhibition of (73±3) % is observed with a mannose trisaccharide containing a glycolipid, whereas this glycolipid did not promote biofilm inhibition activity better than that of arabinomannan glycolipid. The antibiotic supplementation activities of glycolipids on growth and biofilm inhibitions are evaluated. Increases in growth and biofilm inhibitions are observed if the antibiotic is supplemented with glycolipids, which leads to a significant reduction of inhibition concentrations of the antibiotic.

Small-Molecule Inhibition of Bacterial Biofilm

“…smegmatis biofilm and potentiate isoniazid killing (Figure ). Similar studies with synthetic glycolipids and arabinofuranosides were found to interfere with biofilm formation and maturation in M . smegmatis (Figure ).…”

“…Arabinomannan-containing glycolipids have been shown to possess potent antibiofilm activity against M. smegmatis biofilm and potentiate isoniazid killing (Figure 7). 18 Similar studies with synthetic glycolipids and arabinofuranosides were found to interfere with biofilm formation and maturation in M. smegmatis (Figure 7). 19 The synthetic compound 4-hydroxy-2-pyridone is effective against M. smegmatis in biofilm formation.…”