Affiliation:
1. Department of Biology
2. Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, Georgia 30322
Abstract
ABSTRACT
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.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
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