MALBRUNY B, CANU A, BOZDOGAN B, ZARROUK V, FANTIN B, LECLERCQ R; Interscience Conference on Antimicrobial Agents and Chemotherapy.

Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2000 Sep 17-20; 40: 118.

Hosp. Cote de Nacre- Caen Univ., Caen, France

BACKGROUND: Quinupristin-Dalfopristin (Q/D) is active against staphylococci. However mutants resistant to Q/D selected in vivo by this drug have been reported. We have studied two pre- and post-treatment pairs of Staphylococcus aureus susceptible and resistant to Q/D. One pair was isolated in a patient (S. aureus 740 and 740-1) and the other one (S. aureus RP13 and RP13-1) in a rabbit with experimental aortic endocarditis (V. Zarrouk et al., Antimicrob. Agents Chemother., in press).METHODS: The genes for ribosomal proteins L4, L10, L11, L16, L22, and L24, and for domains II and V of the 23S rRNA of S. aureus RP13 and RP13-1 and for protein L22 of S. aureus 740 and 740-1 were sequenced.RESULTS: For the S. aureus 740 and RP13 pairs, MICs of quinupristin (Q) increased from 0.5 to 8 microg/ml and from 2 to 8 microg/ml, and those of Q/D from 0.25 to 2 microg/ml and from 0.5 to 4 microg/ml, respectively. A similar increase was found for MICs of erythromycin. By contrast, MICs of dalfopristin (D) were identical for the pairs of strains. Only alterations in the sequence for L22 protein were found. S. aureus RP13-1 and S. aureus 740-1 displayed a 2 aminoacid deletion (79GT) and a tandem duplication of the sequence AINKRTS in position 102, respectively. The mutated L22 gene of S. aureus RP13-1 was cloned in plasmid pJIM2246 and introduced into the susceptible S. aureus RN4220 strain by transformation. MIC of Q increased from 2 to 4 microg/ml and that of Q/D from 0.25 to 2 microg/ml for the transformant without any change for D. Conclusion: Selection of in vivo Q/D resistance was explained by L22 mutations. These mutations led to a complete or partial loss of synergism between Q and D. Thus, it is inferred that the L22 protein is involved in the synergistic inhibition by the antibiotic combination.KEYWORDS: Quinupristin-dalfopristin; Ribosome; Staphylococcus aureus

Publication Types:

• Meeting Abstracts

Keywords:

• Animals
• Anti-Bacterial Agents
• Base Sequence
• Humans
• Microbial Sensitivity Tests
• Mutation
• Rabbits
• Ribosomal Proteins
• Ribosomes
• Staphylococcus aureus
• Virginiamycin
• dalfopristin
• genetics
• quinupristin
• quinupristin-dalfopristin
• ribosomal protein L4

Other ID:

• GWAIDS0011330

UI: 102248828

From Meeting Abstracts