Temporal variation in antibiotic environments slows down resistance evolution in pathogenic Pseudomonas aeruginosa

Evolutionary Applications

Roderich Roemhild²  Camilo Barbosa²  Robert E. Beardmore¹  Gunther Jansen² 

[1] Biosciences, Geoffrey Pope Building, University of Exeter, Exeter, UK;Evolutionary Ecology and Genetics, University of Kiel, Kiel, Germany

关键词: antibiotic cycling;    antibiotic resistance;    collateral sensitivity;    experimental evolution;    Pseudomonas aeruginosa;    sequential therapy;    temporal variation;   

DOI  :  10.1111/eva.12330

来源: Wiley

【 摘 要 】

Abstract

Antibiotic resistance is a growing concern to public health. New treatment strategies may alleviate the situation by slowing down the evolution of resistance. Here, we evaluated sequential treatment protocols using two fully independent laboratory-controlled evolution experiments with the human pathogen Pseudomonas aeruginosa PA14 and two pairs of clinically relevant antibiotics (doripenem/ciprofloxacin and cefsulodin/gentamicin). Our results consistently show that the sequential application of two antibiotics decelerates resistance evolution relative to monotherapy. Sequential treatment enhanced population extinction although we applied antibiotics at sublethal dosage. In both experiments, we identified an order effect of the antibiotics used in the sequential protocol, leading to significant variation in the long-term efficacy of the tested protocols. These variations appear to be caused by asymmetric evolutionary constraints, whereby adaptation to one drug slowed down adaptation to the other drug, but not vice versa. An understanding of such asymmetric constraints may help future development of evolutionary robust treatments against infectious disease.

【 授权许可】

CC BY   
© 2015 The Authors. Evolutionary Applications published by John Wiley & Sons Ltd.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.