Journal of Antimicrobial Chemotherapy, Vol 39, 7-13, Copyright © 1997 by The British Society for Antimicrobial Chemotherapy
C Cocito, M Di Giambattista, E Nyssen and P Vannuffel
The streptogramins and related antibiotics (the lincosamides and
macrolides) (MLS) are important inhibitors of bacterial protein synthesis.
The key reaction in this process is the formation of a peptide bond between
the growing peptide chain (peptidyl-tRNA) linked to the P-site of the 50S
ribosome and aminoacyl-tRNA linked to the A site. This reaction is
catalysed by the peptidyl transferase catalytic centre of the 50S ribosome.
Type A and B streptogramins in particular have been shown to block this
reaction through the inhibition of substrate attachment to the A and P
sites and inhibition of peptide chain elongation. Synergy between type A
and B components results from conformational changes imposed upon the
peptidyl transferase centre by type A compounds and by inhibition of both
early and late stages of protein synthesis. The conformational change
increases ribosomal affinity for type B streptogramins. Microbial
resistance to the MLSB antibiotics is largely attributable to mutations of
rRNA bases, producing conformational changes in the peptidyl transferase
centre. This can result in resistance to a single inhibitor or to a group
of antibiotics (MLSB). The activity of type A streptogramin is retained
thus explaining the improved inhibitory action of the combined
streptogramins against macrolide and lincosamide-resistant strains.
However, the development of resistance to the streptogramins may be less of
a problem because of the synergic effect of type A and B compounds which
has also been demonstrated in strains resistant to MLSB i.e., high level
resistance to the combined streptogramins is only likely when type A
streptogramin resistance determinants are present along with type B
streptogramin resistance determinants.
ORIGINAL ARTICLES
Inhibition of protein synthesis by streptogramins and related antibiotics
Histology Department, University of Louvain, Medical School, Brussels, Belgium.
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