Selection of resistant bacteria at very low antibiotic concentrations.
Selection of resistant bacteria at very low antibiotic concentrations.
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DOI：
10.1371/journal.ppat.1002158
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发表时间：
2011-07
期刊：
影响因子：
6.7
通讯作者：
Andersson DI
中科院分区：
文献类型：
--
作者：
Gullberg E;Cao S;Berg OG;Ilbäck C;Sandegren L;Hughes D;Andersson DI
抗生素的广泛使用正在选择各种耐药机制，严重挑战我们治疗细菌感染的能力。耐药细菌可以在高浓度的抗生素治疗中选择，但在许多环境中存在的低得多的抗生素浓度在选择中起什么作用仍然很不清楚。在这里，我们使用高度敏感的竞争实验表明，选择耐药细菌发生在极低的抗生素浓度。因此，对于三种临床上重要的抗生素，药物浓度比敏感细菌的最小抑菌浓度低几百倍可以富集耐药细菌，即使以非常低的初始分数存在。我们还表明，从头突变体可以选择在亚MIC浓度的抗生素，我们提供了一个数学模型，预测如何迅速这样的突变体将接管在易感人群。这些结果为耐药性的进化增加了另一个维度，并表明在许多自然环境中发现的低抗生素浓度对于细菌种群的富集和维持耐药性非常重要。由于抗生素在人类和兽医学以及农业中的广泛使用和滥用，抗生素耐药性已经成为一个非常重要的卫生保健问题。目前尚不清楚大多数耐药细菌是在哪里选择的，特别是在治疗或促生长使用期间，自然环境或人/动物体隔室中存在的低抗生素浓度是否对耐药突变体的选择和富集很重要。所提供的数据表明，对于几种临床使用的抗生素，极低的浓度，类似于自然环境中发现的浓度，可以选择耐药细菌。这些结果表明，抗生素释放到环境中可能是一个显着的贡献者的出现和维持的耐药性，并强调引入措施，以减少抗生素污染的重要性。
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. Antibiotic resistance has emerged as a very significant health care problem due to the extensive use and misuse of antibiotics in human and veterinary medicine and in agriculture. It remains unclear where most of the resistant bacteria have been selected, and in particular if the low antibiotic concentrations that are present in natural environments or in human/animal body compartments during therapeutic or growth promotion use, are important for the selection and enrichment of resistant mutants. The presented data shows that for several clinically used antibiotics extremely low concentrations, similar to the concentrations found in natural environments, can select for resistant bacteria. These results suggest that antibiotic release into the environment might be a significant contributor to the emergence and maintenance of resistance and emphasize the importance of introducing measures to reduce antibiotic pollution.
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