Macrolide-resistant Streptococcus pyogenes isolates from Finland, Australia, and the United Kingdom and, more recently, Streptococcus pneumoniae and S. pyogenes strains from the United States were shown to have an unusual resistance pattern to macrolides, lincosamides, and streptogramin B antibiotics. This pattern, referred to as M resistance, consists of susceptibility to clindamycin and streptogramin B antibiotics but resistance to 14- and 15-membered macrolides. An evaluation of the macrolide-lincosamide-streptogramin B resistance phenotypes among our streptococcal strains collected from 1993 to 1995 suggested that this unusual resistance pattern is not rare. Eighty-five percent (n = 66) of the S. pneumoniae and 75% (n = 28) of the S. pyogenes strains in our collection had an M phenotype. The mechanism of M resistance was not mediated by target modification, as isolated ribosomes from a pneumococcal strain bearing the M phenotype were fully sensitive to erythromycin. Further, the presence of an erm methylase was excluded with primers specific for an erm consensus sequence. However, results of studies that determined the uptake and incorporation of radiolabeled erythromycin into cells were consistent with the presence of a macrolide efflux determinant. The putative efflux determinant in streptococci seems to be distinct from the multicomponent macrolide efflux system in coagulase-negative staphylococci. The recognition of the prevalence of the M phenotype in streptococci has implications for sensitivity testing and may have an impact on the choice of antibiotic therapy in clinical practice.

Streptococcus pneumoniae and Streptococcus pyogenes resistant to macrolides but sensitive to clindamycin: a common resistance pattern mediated by an efflux system.

Bacterial resistance to macrolide, lincosamide, and streptogramin antibiotics by target modification.

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1016/0014-5793%2874%2980689-7

Inhibitors of protein synthesis

Structures of Five Antibiotics Bound at the Peptidyl Transferase Center of the Large Ribosomal Subunit

The complete nucleotide sequence of the 23S RNA gene from the rrnB operon of Escherichia coli has been determined. The sequences of both strands of the entire gene were determined, most of the sequence was independently confirmed by use of alternate restriction fragments, and all restriction cuts overlapped. The DNA region corresponding to mature 23S rRNA contains 2904 nucleotides. Kethoxal-reactive sites protected by 30S subunits are found between positions 2300 and 28000, placing the subunit interface in this region of the molecule. The functional importance of this region is further supported by studies by other investigators, including homology with chloroplast and mitochondrial rRNA.

Complete nucleotide sequence of a 23s ribosomal rna gene from escherichia coli

In Escherichia coli there is one binding site per ribosome for lincomycin, chloramphenicol and erythromycin.



These antibiotics act at closely related sites on the 50-S subunit. There are, however, some interesting differences in the properties of the three sites, such as: (a) the apparent possibility of obstructing the lincomycin site without closing the chloramphenicol site, (b) asymmetry of competition effects between chloramphenicol and erythromycin, (c) differential responses to ethanol and (d) differential responses to other antibiotics (puromycin, macrolides, streptogramins A and B and others also acting on the larger ribosome subunit).

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1432-1033.1971.tb01607.x

Substrate-and antibiotic-binding sites at the peptidyl-transferase centre of Escherichia coli ribosomes. Studies on the chloramphenicol, lincomycin, and erythromycin sites

Ramon Torres‐Pinedo

Papers

Substrate-and antibiotic-binding sites at the peptidyl-transferase centre of Escherichia coli ribosomes. Studies on the chloramphenicol, lincomycin, and erythromycin sites