Jun 22, 2005 - The fitness cost of a resistance determinant is the primary parameter that determines its frequency in vivo. ... Mailing address: Department of Micro- ...... ments as a consequence of recurrent infections, repeated mass.
Fitness Cost Due to Mutations in the 16S rRNA Associated with Spectinomycin Resistance in Chlamydia psittaci 6BC Rachel Binet and Anthony T. Maurelli* Department of Microbiology and Immunology, F. Edward He´bert School of Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, Maryland 20814-4799 Received 22 June 2005/Returned for modification 26 July 2005/Accepted 2 August 2005
The fitness cost of a resistance determinant is the primary parameter that determines its frequency in vivo. As a model for analysis of the impact of drug resistance mutations on the intracellular life cycle of Chlamydia spp., we studied the growth of four genetically defined spectinomycin-resistant (Spcr) clonal variants of Chlamydia psittaci 6BC isolated in the plaque assay. The development of each variant was monitored over 46 h postinfection in the absence of drug, either in pure culture or in 1:1 competition with the parent strain. Spcr mutations in the 16S rRNA gene at positions 1191 and 1193 were associated with a marked impairment of C. psittaci biological fitness, and the bacteria were severely outcompeted by the wild-type parent. In contrast, mutations at position 1192 had minor effects on the bacterial life cycle, allowing the resistant isolates to compete more efficiently with the wild-type strain. Thus, mutations with a wide range of fitness costs can be selected in the plaque assay, providing a new strategy for prediction and monitoring of the emergence of antibiotic resistance in chlamydiae. So far, drug resistance has not been a serious threat for the treatment of chlamydial infections. Tetracycline is an effective antichlamydial drug that targets 16S rRNA. Attempts to isolate spontaneous tetracycline-resistant mutants of C. psittaci 6BC revealed a frequency
