Macrolide-Lincosamide-Streptogramin B (MLSB) Resistance
Macrolides are composed of 14 (erythromycin and clarithromycin)-, 15 (azithromycin)-, or 16 (josamycin, spiramycin, and tylosin)-membered lactones to which are attached amino and/or neutral sugars via glycosidic bonds. Erythromycin was introduced in 1952 as the first macrolide antibiotic. The newer derivatives, such as clarithromycin and azithromycin, have improved intracellular and tissue penetration, are more stable, are better absorbed, have a lower incidence of gastrointestinal side effects, and are less likely to interact with other drugs. They are useable against a wider range of infectious bacteria, such as Legionella, Chlamydia, Haemophilus, and some Mycobacterium species (not M. tuberculosis).
Macrolides inhibit protein synthesis by stimulating dissociation of the peptidyl-tRNA molecule from the ribosomes during elongation. This results in chain termination and a reversible stoppage of protein synthesis. The first mechanism of macrolide resistance described was due to posttranscriptional modification of the 23S rRNA by the adenine-N6 methyltransferase. These enzymes add one or two methyl groups to a single adenine (A2058 in Escherichia coli) in the 23S rRNA moiety.
The binding site in the 50S ribosomal subunit for erythromycin overlaps the binding site of the newer macrolides, as well as the structurally unrelated lincosamides and streptogramin B antibiotics. The modification by methylase reduces the binding of all three classes of antibiotics, which results in resistance against (MLSB) antibiotics. The rRNA methylases (erm) are the best studied among macrolide resistance mechanisms. However, a variety of other mechanisms have been described which also confer resistance. Many of these alternative mechanisms of resistance confer resistance to only one or two of the antibiotic classes of the MLSB antibiotics, such as ATP-binding transporters (ABC), major facilitator transporters, esterases, hydrolases, transferases and phosphorylases.
Here is a list of MLSB resistance types