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Antimicrobial Agents and Chemotherapy, February 2007, p. 412-416, Vol. 51, No. 2
0066-4804/07/$08.00+0     doi:10.1128/AAC.01161-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Fitness Costs of Fluoroquinolone Resistance in Streptococcus pneumoniae{triangledown}

Daniel E. Rozen,1* Lesley McGee,2 Bruce R. Levin,1 and Keith P. Klugman2

Department of Biology,1 Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, Georgia 303222

Received 15 September 2006/ Returned for modification 15 October 2006/ Accepted 13 November 2006

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.

* Corresponding author. Present address: Faculty of Life Sciences, University of Manchester, Michael Smith Building, Oxford Road, Manchester M13 9PT, United Kingdom. Phone: 44-161-275-5094. Fax: 44-161-275-5082. E-mail: daniel.rozen{at}manchester.ac.uk.

{triangledown} Published ahead of print on 20 November 2006.

Antimicrobial Agents and Chemotherapy, February 2007, p. 412-416, Vol. 51, No. 2
0066-4804/07/$08.00+0     doi:10.1128/AAC.01161-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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