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.
Wright
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EL
Department of Microbiology and Immunology, Texas College of Osteopathic Medicine, Fort Worth 76107.
Barrow
W W
WW
D001345:Autoradiography; D002851:Chromatography, High Pressure Liquid; D002855:Chromatography, Thin Layer; D003847:Deoxyglucose / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006017:Glycolipids / Q000032:analysis / Q000378:metabolism*; D066298:In Vitro Techniques; D008358:Mannose / Q000032:analysis; D008715:Methionine / Q000032:analysis; D009162:Mycobacterium avium / Q000187:drug effects* / Q000378:metabolism; D010649:Phenylalanine / Q000032:analysis
D006017:Glycolipids; D010649:Phenylalanine; D003847:Deoxyglucose; D008715:Methionine; D008358:Mannose