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Antimicrobial Agents and Chemotherapy, December 2007, p. 4361-4365, Vol. 51, No. 12
0066-4804/07/$08.00+0     doi:10.1128/AAC.00672-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Activity of the Novel Macrolide BAL19403 against Ribosomes from Erythromycin-Resistant Propionibacterium acnes

Basilea Pharmaceutica AG, Basel, Switzerland

Received 23 May 2007/ Returned for modification 22 June 2007/ Accepted 26 September 2007

BAL19403 is a macrolide antibiotic from a novel structural class with potent activity against propionibacteria in vitro. The antibacterial spectrum of BAL19403 covers clinical isolates with mutations in the 2057 to 2059 region of 23S rRNA that confer resistance to erythromycin and clindamycin. The basis of this improved activity was investigated by ribosome binding assays and by a coupled transcription and translation assay. The latter was specifically developed for the use of ribosomes from Propionibacterium acnes. BAL19403 inhibited protein expression by ribosomes from erythromycin-sensitive and erythromycin-resistant P. acnes with similar potencies if the resistance was due to G2057A or A2058G mutations. BAL19403 showed a >10-fold higher activity than erythromycin against ribosomes from a strain with the erm(X) gene. Erm(X) confers high levels of macrolide and lincosamide resistance by dimethylation of A2058. Assays with such ribosomes showed that BAL19403 was potent enough to inhibit half of the total activity with a 50% inhibitory concentration very close to the value measured with erythromycin-sensitive ribosomes. We concluded from our data that the P. acnes strain with the erm(X) gene had a mixed population of ribosomes, with macrolide-sensitive and macrolide-resistant species.

Published ahead of print on 8 October 2007.