Mechanism of action of spiramycin and other macrolides

Abstract

Macrolide antibiotics constitute a group of 12 to 16-membered lactone rings substituted with one or more sugar residues, some of which may be amino sugars. They inhibit bacterial protein synthesis both in vivo and in vitro with varying potencies. Macrolides are generally bacteriostatic, although some of these drugs may be bactericidal at very high concentrations. The mechanism of action of macrolides has been a matter of controversy for some time. Spiramycin, a 16-membered macrolide, inhibits translocation by binding to bacterial 50S ribosomal subunits with an apparent 1:1 stoichiometry. This antibiotic is a potent inhibitor of the binding to the ribosome of both donor and acceptor substrates. Spiramycin induces rapid breakdown of polyribosomes, an effect which has formerly been interpreted as occurring by normal ribosomal run-off followed by an antibiotic-induced block at or shortly after initiation of a new peptide. However, there is now convincing evidence that spiramycin, and probably all macrolides, act primarily by stimulating the dissociation of peptidyl-tRNA from ribosomes during translocation. Although the ribosomes of both Gram-positive and Gram-negative organisms are susceptible to macrolides, these antibiotics are mainly used against Gram-positive bacteria since they are unable to enter the porins of Gram-negative bacteria. Resistance to macrolides in clinical isolates is most frequently due to post-transcriptional methylation of an adenine residue of 23S ribosomal RNA, which leads to co-resistance to macrolides, lincosamides and streptogramins type B (the so-called MLSB phenotype). Other mechanisms of resistance involving cell impermeability or drug inactivation have been detected in Staphylococcus spp. and Escherichia coli. These strains are resistant to 14-membered macrolides (erythromycin and oleandomycin) but remain susceptible to spiramycin.

Plasmid Curing Assay in Clinical Isolates of Antibiotic Resistant Acinetobacter baumannii

“…Recently multidrug resistance character of Acinetobacter considered as a major problem for commercially available antibiotic (Bergogne-Berezin, 2007;Dijkshoorn et al, 2007). Among all species of Acinetobacter, A. baumannii has become a significant pathogen, especially in the intensive care unit (Bauer et al, 1966;Brisson-Noel et al, 1988;Courvalin, 1994;Beige et al, 2015). Survival of this bacterium in the hospital, especially in the ICU seems to be related to their ability of acquiring antibiotic resistant genes.…”

Analgesic and Anti-inflammatory Activity of Roxithromycin and Erythromycin, Alone and in Combination with Ibuprofen: An Animal Study

“…Macrolide antibiotics constitute a group of 12 to 16-membered lactone rings substituted with one or more sugar residues 1 . Erythromycin, the first macrolide to be described, was first isolated in 1952 2 ; since then it has established itself as one of the safest antibiotics in use and an effective alternative to penicillin for the treatment of and prophylaxis against Gram positive infections of the skin, soft tissues and respiratory tract, and agent of choice for treating infections caused by Mycoplasma pneumoniae, Bordetella pertussis and Legionella sp 3 .…”

Mutation in 23S rRNA Responsible for Resistance to 16-Membered Macrolides and Streptogramins in Streptococcus pneumoniae

“…They act by binding to the 50S subunit of bacterial ribosomes and inhibit protein synthesis by blocking elongation of the nascent peptide chain (2,10).…”