Fitness Tradeoffs of Antibiotic Resistance in Extraintestinal Pathogenic Escherichia coli

被引:46
作者
Basra, Prabh [1 ]
Alsaadi, Ahlam [1 ]
Bernal-Astrain, Gabriela [1 ]
O'Sullivan, Michael Liam [1 ]
Hazlett, Bryn [1 ]
Clarke, Leah Marie [1 ]
Schoenrock, Andrew [2 ,3 ]
Pitre, Sylvain [3 ]
Wong, Alex [1 ]
机构
[1] Carleton Univ, Dept Biol, Ottawa, ON, Canada
[2] Carleton Univ, Sch Comp Sci, Ottawa, ON, Canada
[3] Carleton Univ, Res Comp Serv, Ottawa, ON, Canada
来源
GENOME BIOLOGY AND EVOLUTION | 2018年 / 10卷 / 02期
基金
加拿大自然科学与工程研究理事会;
关键词
antibiotic resistance; trade-off; whole-genome sequencing; compensatory evolution; epistasis; ANTIMICROBIAL RESISTANCE; QUINOLONE RESISTANCE; BIOLOGICAL COST; COMPENSATORY MUTATIONS; EVOLUTION; REDUCTION; DIVERSITY; COMMUNITY; PLASMID; OFFS;
D O I
10.1093/gbe/evy030
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
Evolutionary trade-offs occur when selection on one trait has detrimental effects on other traits. In pathogenic microbes, it has been hypothesized that antibiotic resistance trades off with fitness in the absence of antibiotic. Although studies of single resistance mutations support this hypothesis, it is unclear whether trade-offs are maintained over time, due to compensatory evolution and broader effects of genetic background. Here, we leverage natural variation in 39 extraintestinal clinical isolates of Escherichia coli to assess trade-offs between growth rates and resistance to fluoroquinolone and cephalosporin antibiotics. Whole-genome sequencing identifies a broad range of clinically relevant resistance determinants in these strains. We find evidence for a negative correlation between growth rate and antibiotic resistance, consistent with a persistent trade-off between resistance and growth. However, this relationship is sometimes weak and depends on the environment in which growth rates are measured. Using in vitro selection experiments, we find that compensatory evolution in one environment does not guarantee compensation in other environments. Thus, even in the face of compensatory evolution and other genetic background effects, resistance may be broadly costly, supporting the use of drug restriction protocols to limit the spread of resistance. Furthermore, our study demonstrates the power of using natural variation to study evolutionary trade-offs in microbes.
引用
收藏
页码:667 / 679
页数:13
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