Selection of Resistant Bacteria at Very Low Antibiotic Concentrations

PLoS Pathogens

Linus Sandegren¹  Dan I. Andersson¹  Erik Gullberg¹  Diarmaid Hughes¹  Carolina Ilbäck¹  Sha Cao¹  Otto G. Berg² 

[1] Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden;Department of Molecular Evolution, Uppsala University, Uppsala, Sweden

关键词: Antibiotic resistance;    Antibiotics;    Tetracyclines;    Streptomycin;    Natural selection;    Fluorescence competition;    Salmonella typhimurium;    Yellow fluorescent protein;   

DOI  :  10.1371/journal.ppat.1002158

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

The widespread use of antibiotics is selecting for a variety of resistance mechanisms that seriously challenge our ability to treat bacterial infections. Resistant bacteria can be selected at the high concentrations of antibiotics used therapeutically, but what role the much lower antibiotic concentrations present in many environments plays in selection remains largely unclear. Here we show using highly sensitive competition experiments that selection of resistant bacteria occurs at extremely low antibiotic concentrations. Thus, for three clinically important antibiotics, drug concentrations up to several hundred-fold below the minimal inhibitory concentration of susceptible bacteria could enrich for resistant bacteria, even when present at a very low initial fraction. We also show that de novo mutants can be selected at sub-MIC concentrations of antibiotics, and we provide a mathematical model predicting how rapidly such mutants would take over in a susceptible population. These results add another dimension to the evolution of resistance and suggest that the low antibiotic concentrations found in many natural environments are important for enrichment and maintenance of resistance in bacterial populations.

【 授权许可】

CC BY