Stochastic Bacterial Population Dynamics Prevent The Emergence Of Antibiotic Resistance

Understanding how antibiotic exposure impacts the evolution of resistance is key to optimizing antibiotic treatment strategies. The conventional approach to this problem is to measure the range of antibiotic concentrations over which resistance is selectively favoured – the “mutant selection window”. Here we take an alternative approach by investigating how antibiotic concentration impacts de novo establishment of resistance from single cells of a streptomycin-resistant Pseudomonas aeruginosa strain. We show that demographic stochasticity prevents outgrowth of resistant cells with >95% probability across ~90% of the range of streptomycin concentrations where resistance is selectively favoured. This effect occurs because exposure to streptomycin extends lag time and increases the mortality rate of streptomycin-resistant cells. Our study highlights fundamental differences between the processes that drive emergence versus spread of resistance. It suggests that moderate doses of antibiotics, within the traditional mutant selection window, may effectively prevent emergence of resistance in cases where transmission of resistant strains is negligible, for instance when using new antibiotics

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