Fitness costs of fluoroquinolone resistance in Streptococcus pneumoniae.
The fitness cost of the genes responsible for resistance to fluoroquinolones in clinical isolates of Streptococcus pneumoniae were estimated in vitro in a common genetic background. Naturally occurring parC, parE, and gyrA loci containing mutations in the quinolone-resistance-determining regions were introduced by transformation into S. pneumoniae strain R6 individually and in combinations. The fitness of these transformants was estimated by pairwise competition experiments with a common R6 strain. On average, single par and gyr mutants responsible for low-level MIC resistance (first-step resistance) impose a fitness burden of approximately 8%. Some of these mutants engender no measurable cost, while one, a parE mutant, reduces the fitness of these bacteria by more than 40%. Most interestingly, the addition of the second par or gyr mutations required for clinically significant, high-MIC fluoroquinolone resistance does not increase the fitness burden imposed by these single genes and can even reduce it. We discuss the implications of these results for the epidemiology of fluoroquinolone resistance and the evolution of acquired resistance in treated patients.
Rozen
Daniel E
DE
Department of Biology, Rollins School of Public Health, Emory University, Atlanta, GA 30322, USA. daniel.rozen@manchester.ac.uk
McGee
Lesley
L
Levin
Bruce R
BR
Klugman
Keith P
KP
D027081:DNA Gyrase / Q000235:genetics; D027101:DNA Topoisomerase IV / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D024841:Fluoroquinolones / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D009154:Mutation; D011008:Pneumococcal Infections / Q000188:drug therapy / Q000382:microbiology*; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000235:genetics*; D014169:Transformation, Bacterial
D024841:Fluoroquinolones; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase