New targets for the mechanism of action of antibiotics active against gram-positive cocci.
The main mechanisms of resistance to beta-lactams in gram-positive cocci include either the production of beta-lactamases or alterations in the molecular targets of these antibiotics, the penicillin binding proteins (PBPs). In spite of the appearance of new beta-lactams, more stable to the hydrolytic activity of beta-lactamases or with higher affinity for PBPs, no substantial progress in improving the activity against gram-positive has been achieved. In addition to the search for new beta-lactams it would be of interest to find molecules directed against new targets of the cell wall of gram-positive bacteria (i.e. teichoic acids and lipoteichoic acid) of which up to now no specific inhibitor is known. These two wall polymers are thought to be essential for cell survival within the host. Among new inhibitors a new antibiotic belonging to the class of acid lipopeptides called daptomycin (LY146032), and active against gram-positive seems of particular interest. Our studies demonstrate that daptomycin is a specific inhibitor of lipoteichoic acid synthesis.
Canepari
P
P
Istituto di Microbiologia dell'Università di Verona, Italy.
Fontana
R
R
Satta
G
G
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002470:Cell Survival; D017576:Daptomycin / Q000494:pharmacology; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy*; D008070:Lipopolysaccharides / Q000494:pharmacology; D013682:Teichoic Acids / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D008070:Lipopolysaccharides; D013682:Teichoic Acids; C009900:lipoteichoic acid; D017576:Daptomycin