摘要
The long-term persistence of antibiotic resistance in the environment, especially in drinking water, is a public health concern. Expression of an efflux pump, an important mechanism of resistance to antibiotics, usually confers a fitness cost in bacteria. In this study, we aimed to determine why antibiotic resistance conferred by overexpression of an efflux pump persisted in low-nutrient environments(TOC < 10 mg/L) such as drinking and source water in which antibiotic selective pressure might be very low or even absent.Competition experiments between wild-type Pseudomonas aeruginosa and ciprofloxacinresistant mutants revealed that the fitness cost of ciprofloxacin resistance significantly decreased(p < 0.05) under low-nutrient(0.5 mg/L total organic carbon(TOC)) relative to high-nutrient(500 mg/L TOC) conditions. Mechanisms underlying this fitness cost were analyzed. The mexD gene expression in resistant bacteria(cip3 strain) was significantly lower(p < 0.05) in low-nutrient conditions, with 10 mg/L TOC((8.01 ± 0.82)-fold), than in high-nutrient conditions, with 500 mg/L TOC((48.89 ± 4.16)-fold). Moreover, rpoS gene expression in resistant bacteria((1.36 ± 0.13)-fold) was significantly lower(p < 0.05) than that in the wild-type strain((2.78 ± 0.29)-fold) under low-nutrient conditions(10 mg/L TOC),suggesting a growth advantage. Furthermore, the difference in metabolic activity between the two competing strains was significantly smaller(p < 0.05) in low-nutrient conditions(5 and 0.5 mg/L TOC). These results suggest that nutrient levels are a key factor in determining the persistence of antibiotic resistance conferred by efflux pumps in the natural environment with trace amounts or no antibiotics.
The long-term persistence of antibiotic resistance in the environment, especially in drinking water, is a public health concern. Expression of an efflux pump, an important mechanism of resistance to antibiotics, usually confers a fitness cost in bacteria. In this study, we aimed to determine why antibiotic resistance conferred by overexpression of an efflux pump persisted in low-nutrient environments（TOC < 10 mg/L） such as drinking and source water in which antibiotic selective pressure might be very low or even absent.Competition experiments between wild-type Pseudomonas aeruginosa and ciprofloxacinresistant mutants revealed that the fitness cost of ciprofloxacin resistance significantly decreased（p < 0.05） under low-nutrient（0.5 mg/L total organic carbon（TOC）） relative to high-nutrient（500 mg/L TOC） conditions. Mechanisms underlying this fitness cost were analyzed. The mexD gene expression in resistant bacteria（cip3 strain） was significantly lower（p < 0.05） in low-nutrient conditions, with 10 mg/L TOC（（8.01 ± 0.82）-fold）, than in high-nutrient conditions, with 500 mg/L TOC（（48.89 ± 4.16）-fold）. Moreover, rpoS gene expression in resistant bacteria（（1.36 ± 0.13）-fold） was significantly lower（p < 0.05） than that in the wild-type strain（（2.78 ± 0.29）-fold） under low-nutrient conditions（10 mg/L TOC）,suggesting a growth advantage. Furthermore, the difference in metabolic activity between the two competing strains was significantly smaller（p < 0.05） in low-nutrient conditions（5 and 0.5 mg/L TOC）. These results suggest that nutrient levels are a key factor in determining the persistence of antibiotic resistance conferred by efflux pumps in the natural environment with trace amounts or no antibiotics.
基金
supported by the National Natural Science Foundation of China(Nos.51708534,51678551,and 51478450)
the National Key Research and Development Program of China-International collaborative project from the Ministry of Science and Technology(No.2017YFE0107300)
the Xiamen Major Science and Technology Project(No.3502Z20171003)
K.C.Wong Education Foundation
