TY - JOUR
T1 - Compensation of fitness costs and reversibility of antibiotic resistance mutations
AU - Zur Wiesch, Pia Schulz
AU - Engelstädter, Jan
AU - Bonhoeffer, Sebastian
PY - 2010/5
Y1 - 2010/5
N2 - Strains of bacterial pathogens that have acquired mutations conferring antibiotic resistance often have a lower growth rate and are less invasive or transmissible initially than their susceptible counterparts. However, fitness costs of resistance mutations can be ameliorated by secondary site mutations. These so-called compensatory mutations may restore fitness in the absence and/or presence of antimicrobials. We review literature data and show that the fitness gains in the absence and presence of antibiotic treatment need not be correlated. The aim of this study is to gain a better conceptual grasp of how compensatory mutations with different fitness gains affect evolutionary trajectories, in particular reversibility. To this end, we developed a theoretical model with which we consider both a resistance and a compensation locus. We propose an intuitively understandable parameterization for the fitness values of the four resulting genotypes (wild type, resistance mutation only, compensatory mutation only, and both mutations) in the absence and presence of treatment. The differential fitness gains, together with the turnover rate and the mutation rate, strongly affected the success of antibacterial treatment, reversibility, and long-term abundance of resistant strains. We therefore propose that experimental studies of compensatory mutations should include fitness measurements of all possible genotypes in both the absence and presence of an antibiotic.
AB - Strains of bacterial pathogens that have acquired mutations conferring antibiotic resistance often have a lower growth rate and are less invasive or transmissible initially than their susceptible counterparts. However, fitness costs of resistance mutations can be ameliorated by secondary site mutations. These so-called compensatory mutations may restore fitness in the absence and/or presence of antimicrobials. We review literature data and show that the fitness gains in the absence and presence of antibiotic treatment need not be correlated. The aim of this study is to gain a better conceptual grasp of how compensatory mutations with different fitness gains affect evolutionary trajectories, in particular reversibility. To this end, we developed a theoretical model with which we consider both a resistance and a compensation locus. We propose an intuitively understandable parameterization for the fitness values of the four resulting genotypes (wild type, resistance mutation only, compensatory mutation only, and both mutations) in the absence and presence of treatment. The differential fitness gains, together with the turnover rate and the mutation rate, strongly affected the success of antibacterial treatment, reversibility, and long-term abundance of resistant strains. We therefore propose that experimental studies of compensatory mutations should include fitness measurements of all possible genotypes in both the absence and presence of an antibiotic.
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U2 - 10.1128/AAC.01460-09
DO - 10.1128/AAC.01460-09
M3 - Article
C2 - 20176903
AN - SCOPUS:77951223398
SN - 0066-4804
VL - 54
SP - 2085
EP - 2095
JO - Antimicrobial agents and chemotherapy
JF - Antimicrobial agents and chemotherapy
IS - 5
ER -