Sander Peter, Springer Burkhard, Prammananan Therdsak, Sturmfels Antje, Kappler Martin, Pletschette Michel, Böttger Erik C
Institut für Medizinische Mikrobiologie, Universität Zürich, CH-8028 Zürich, Switzerland.
Antimicrob Agents Chemother. 2002 May;46(5):1204-11. doi: 10.1128/AAC.46.5.1204-1211.2002.
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.
为研究细菌染色体耐药性突变的代价，我们调查了赋予对影响细菌蛋白质合成的不同类抗生素（氨基环醇类、2-脱氧链霉胺类、大环内酯类）耐药性的突变的适合度代价。我们使用了一个基于体外竞争试验的模型系统，该试验使用明确的耻垢分枝杆菌实验室突变体；通过遗传技术引入选定的突变，以解决补偿性突变改善耐药代价的可能性。我们发现，所研究的染色体耐药性突变通常仅具有较小的适合度代价；补偿性突变不参与低成本或无成本的耐药性突变。当考虑临床分离株中发现的耐药性突变时，似乎会选择那些在体外竞争试验中适合度代价很小或没有适合度代价的突变。这些结果与将抗生素消耗量的降低与耐药性水平的下降联系起来的预期相悖。
