Lipoteichoic acid as a target for antimicrobial action.
Daptomycin, a lipopeptide antibiotic active against gram-positive bacteria, has been found to inhibit lipoteichoic acid (LTA) synthesis as a consequence of membrane binding in the presence of Ca2+. The present study shows that among the bacterial-membrane components, daptomycin binds the protein fraction with a noncovalent bond, as suggested by the instability of the bond in the presence of an ionic detergent such as sodium dodecyl sulfate. Analysis of membrane proteins by isoelectric focusing electrophoresis reveals that 5 bands with isoelectric points ranging from 5.9 to 6.2 bind radioactive daptomycin. These proteins are therefore called daptomycin-binding proteins. In an attempt to correlate these proteins with the main inhibition observed in LTA synthesis, two-dimensional thin-layer chromatography of lipids synthesized during daptomycin treatment was performed. A 3-fold increase in diglucosyl diacylglycerol is demonstrated, while the compounds phosphatidyl-alpha-kojibiosyldiacylglycerol, glycerophosphophosphatidyl-alpha-kojibiosyldiacyl glycerol, and glycerophosphokojibiosyldiacylglycerol, which follow diglucosyl diacylglycerol in LTA synthesis, decrease progressively with time during the course of daptomycin treatment.
Canepari
P
P
Istituto di Microbiologia, Universitá di Verona, Italy.
Boaretti
M
M
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects* / Q000378:metabolism*; D017576:Daptomycin / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D013682:Teichoic Acids / Q000037:antagonists & inhibitors / Q000096:biosynthesis*
D000900:Anti-Bacterial Agents; D008070:Lipopolysaccharides; D013682:Teichoic Acids; C009900:lipoteichoic acid; D017576:Daptomycin