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Fitness Cost of Chromosomal Drug Resistance-Conferring Mutations

機譯：染色體耐藥性突變的適應(yīng)性成本

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摘要

To study the cost of chromosomal drug resistance mutations to bacteria, we investigated the fitness cost of mutations that confer resistance to different classes of antibiotics affecting bacterial protein synthesis (aminocyclitols, 2-deoxystreptamines, macrolides). We used a model system based on an in vitro competition assay with defined Mycobacterium smegmatis laboratory mutants; selected mutations were introduced by genetic techniques to address the possibility that compensatory mutations ameliorate the resistance cost. We found that the chromosomal drug resistance mutations studied often had only a small fitness cost; compensatory mutations were not involved in low-cost or no-cost resistance mutations. When drug resistance mutations found in clinical isolates were considered, selection of those mutations that have little or no fitness cost in the in vitro competition assay seems to occur. These results argue against expectations that link decreased levels of antibiotic consumption with the decline in the level of resistance.
機譯：為了研究染色體對細菌的耐藥性突變的成本，我們調(diào)查了賦予對影響細菌蛋白質(zhì)合成的不同種類抗生素（氨基環(huán)糖醇，2-脫氧鏈胺胺，大環(huán)內(nèi)酯類）耐藥的突變的適應(yīng)性成本。我們使用了基于體外競爭測定法的模型系統(tǒng)，該系統(tǒng)具有已定義的恥垢分枝桿菌實驗室突變體；通過遺傳技術(shù)引入選擇的突變，以解決補償性突變改善抗藥性的可能性。我們發(fā)現(xiàn)，所研究的染色體耐藥性突變通常只具有很小的適應(yīng)性成本。補償性突變不涉及低成本或無成本的抗性突變。當(dāng)考慮在臨床分離物中發(fā)現(xiàn)的耐藥性突變時，似乎選擇了在體外競爭試驗中幾乎沒有適應(yīng)成本的突變。這些結(jié)果違背了將抗生素消耗量下降與耐藥性下降聯(lián)系起來的預(yù)期。

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