[Macrolides, lincosamides, streptogramines (MLS): mechanisms of action and resistance].

Abstract

Macrolides, lincosamides and streptogramines are distinct antibiotic (AB) families, with different chemical structure, but with similar antibacterial spectre and mechanisms. Macrolides are natural products of secondary metabolism of several species of actynomyces; they represent a group of compounds with a lactonic ring of variable dimensions (12-22 atoms of C) that can bind, by means of glycosidic bonds, sacharridic and/or amino-sacharridic structures. Most of the MLS antibiotics are bacteriostatic. Their mechanisms consist in inhibiting protein synthesis. the target being 50 S subunit of the bacterial ribosome, the binding sites being different for the different MLS classes. Erythromycin (E) was introduced in therapy in 1952; quickly, several bacterial genera started developing resistance to E. Strains resistant to E were as well resistant to all macrolides and other antibiotics with different structures--lincosamides and streptogramines B--resistance phenotype called MLSB. The main molecular mechanisms for bacterial resistance to MLS are: (1) Target modification, coded by erm genes (>12 classes). In Gram-positive cocii MLSB resistance, regardless of erm gene, can be: inducible (i MLSB)--when the presence of the inductor AB is necessary for methylation enzyme production; constitutive (c MLSB)--when the methylation enzyme is continuously produced Distinction between iMLSB and cMLSB can be easily appreciated based on the phenotypic expression of bacteria. In streptococci--all MLSB antibiotics can act as methylase inductors. (2) The decrease of AB intracellular concentration by active efflux, coded by mef genes--also called M resistance phenotype, low level resistance (LLR). (3) AB inactivation (enzymatic modification of AB); there are different resistance phenotypes: MLSB +SA and L phenotype (in staphyilococci) or SA4 phenotype and L phenotype (in enterococci).