Inhibition of glycopeptidolipid synthesis resulting from treatment of Mycobacterium avium with 2-deoxy-D-glucose

Exponentially growing cultures of Mycobacterium avium complex serovar 4 were treated with 2-deoxy-D-glucose (2-DDG) and incubated with radiolabelled components which incorporate into the serovar-specific glycopeptidolipids (GPL) associated with the L1 layer. Following treatment with the drug, radiolabelled lipids were extracted from the mycobacteria and examined by thin-layer chromatography, high performance liquid chromatography and autoradiography to determine the percent distribution of radioactivity in the GPL and other related lipids. Treatment of serovar 4 with 2-DDG resulted in a dose-dependent inhibition of GPL biosynthesis, as judged by a reduction in the incorporation of radiolabelled phenylalanine, mannose and methionine into the GPL. In addition, a concomitant accumulation of at least two phenylalanine-containing lipopeptides was observed in cells treated with 2-DDG. Cultivation of serovar 4 in the presence of 2-deoxy-D-1,2-(3)H-glucose did not result in internal radiolabelling of the GPL, indicating that 2-DDG was not being incorporated into the GPL as an analogue of mannose, but rather was acting as a metabolic inhibitor of GPL biosynthesis.