MCNICHOLAS PM, MANN PA, NAJARIAN DJ, CHAU AS, BLACK TA, AARESTRUP FA, HARE RS; Interscience Conference on Antimicrobial Agents and Chemotherapy.

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2000 Sep 17-20; 40: 534.

Schering-Plough Res. Inst., Kenilworth, NJ

Evernimicin, an antibiotic with activity against gram-positive bacteria, binds a single high affinity site on the 50 S subunit and inhibits translation. These observations are supported by an analysis of evernimicin resistant mutants. Resistant mutants have been identified in a number of organisms including Staphylococcus aureus, Streptococcus pneumoniae, Enterococcus faecium and E. faecalis. The most frequent cause of low level resistance is a missense mutation in the rplP gene which encodes the 50 S subunit protein L16. L16 has been implicated in aminoacyl-tRNA binding and peptidyltransferase activity. In S. aureus, substitutions in residue 51 of L16 reduced both drug binding to the ribosome and cellular accumulation of evernimicin. Resistance in S. pneumoniae results from either mutations in rplP (residues 51 and 52) or mutations in the rDNA operons. Four independent mutations were mapped to the peptidyltransferase center of the 23S rRNA and two of these mutations were located in a stem loop that interacts with L16. Strains of E. faecium and E. faecalis, isolated from animals on the basis of their avilamycin resistance, exhibited cross resistance to low levels of evernimicin. Of the 36 strains analyzed, 35 had single amino acid changes in either residue 52 or 56 of L16. One E. faecium strain exhibited high level evernimicin resistance (MIC >256 mcg/ml). We cloned a novel rRNA methylase gene, designated emtA for evernimicin methyl transferase, and determined its product was responsible for the observed resistance. EmtA specifically methylated 23 S rRNA, as a result the modified ribosomes neither bound evernimicin or were inhibited in cell free translation assays. emtA, along with ermB, was localized to a transmissible plasmid.KEYWORDS: Evernimicin; Methylase; Resistance

Publication Types:

• Meeting Abstracts

Keywords:

• Aminoglycosides
• Anti-Bacterial Agents
• Enterococcus faecium
• Methyltransferases
• Microbial Sensitivity Tests
• Mutation
• Plasmids
• Protein Biosynthesis
• RNA, Ribosomal
• Ribosomal Proteins
• Ribosomes
• Staphylococcus aureus
• Streptococcus pneumoniae
• everninomicin
• genetics
• rRNA (adenosine-O-2'-)methyltransferase
• ribosomal protein L16

Other ID:

• GWAIDS0009498

UI: 102246996

From Meeting Abstracts