Low nutrient levels as drinking water conditions can reduce the fitness cost of efflux pump-mediated

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The long-term persistence of antibiotic resistance in the environment,especially in drinking water,is a public health conc.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 (cip_3 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.
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