Oct 31, 2018

Stochastic bacterial population dynamics prevent the emergence of antibiotic resistance from single cells

BioRxiv : the Preprint Server for Biology
Helen K. Alexander, Craig MacLean

Abstract

A better understanding of how antibiotic exposure impacts the evolution of resistance is crucial for designing more sustainable treatment strategies. The conventional approach to relating antibiotic dose to resistance evolution within a bacterial population is to measure the range of concentrations over which resistant strain(s) are selectively favoured over a sensitive strain - the "mutant selection window". Here, we instead investigate how antibiotic concentration impacts the initial establishment of resistance from single cells, mimicking the clonal expansion of a resistant lineage following mutation or horizontal gene transfer. Using two Pseudomonas aeruginosa strains carrying distinct resistance plasmids, we show that single resistant cells have <5% probability of outgrowth at antibiotic concentrations as low as 1/8th of the resistant strain's minimum inhibitory concentration. This low probability of establishment is due to detrimental effects of antibiotics on resistant cells, coupled with the inherently stochastic nature of cell division and death on the single-cell level, which leads to loss of many nascent resistant lineages. Our findings suggest that moderate doses of antibiotics, within the traditional mutant selecti...Continue Reading

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Mentioned in this Paper

Study
Pseudomonas aeruginosa (antigen)
Pathogenic Organism
Streptomycin
Pseudomonas aeruginosa
Disease Transmission
Minimum Inhibitory Concentration Measurement
Resistance Process
Mutant
Neuronal Outgrowth

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