Death and population dynamics affect mutation rate estimates and evolvability under stress in bacteria

PLoS Biology
Antoine Frenoy, Sebastian Bonhoeffer

Abstract

The stress-induced mutagenesis hypothesis postulates that in response to stress, bacteria increase their genome-wide mutation rate, in turn increasing the chances that a descendant is able to better withstand the stress. This has implications for antibiotic treatment: exposure to subinhibitory doses of antibiotics has been reported to increase bacterial mutation rates and thus probably the rate at which resistance mutations appear and lead to treatment failure. More generally, the hypothesis posits that stress increases evolvability (the ability of a population to generate adaptive genetic diversity) and thus accelerates evolution. Measuring mutation rates under stress, however, is problematic, because existing methods assume there is no death. Yet subinhibitory stress levels may induce a substantial death rate. Death events need to be compensated by extra replication to reach a given population size, thus providing more opportunities to acquire mutations. We show that ignoring death leads to a systematic overestimation of mutation rates under stress. We developed a system based on plasmid segregation that allows us to measure death and division rates simultaneously in bacterial populations. Using this system, we found that a s...Continue Reading

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Citations

May 19, 2019·The Journal of Antimicrobial Chemotherapy·Ana I Rodríguez-RosadoJesús Blázquez
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Software Mentioned

FALCOR ( Fluctuation AnaLysis CalculatOR )
ATREYU
Zenodo
rSalvador
bzRates
FALCOR

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