Nature:细菌产生抗药性的机制

2010-09-02 00:00 · Aries

对抗菌素有抗药性的细菌菌种的出现,是临床环境中一个越来越大的威胁,但人们对它们出现的过程却不是很了解。利用暴露于浓度不断增大的氟喹诺酮抗菌药“诺氟沙星”的一个大肠杆菌连续培养物所做实验表明,少数自然出现的抗药变体能保护其种群的绝大部分。这些具有高度抗药性的分离菌种产生信号作用分


对抗菌素有抗药性的细菌菌种的出现,是临床环境中一个越来越大的威胁,但人们对它们出现的过程却不是很了解。利用暴露于浓度不断增大的氟喹诺酮抗菌药“诺氟沙星”的一个大肠杆菌连续培养物所做实验表明,少数自然出现的抗药变体能保护其种群的绝大部分。这些具有高度抗药性的分离菌种产生信号作用分子“吲哚”,它能激发易感皮肤中的药物外排泵和其他保护机制。

这种利他行为使较弱的成分能够存活,并有机会进行有益的突变。对细菌的细胞内通信的使用情况进行更多研究,对于用以控制抗药性细菌感染的临床干预手段的合理设计可能会被证明是有价值的。本期封面上的“红十字”图是用数字化手段从大肠杆菌种群的图像生成的。

生物谷推荐英文摘要:

Nature doi:10.1038/nature09354

Bacterial charity work leads to population-wide resistance

Henry H. Lee ,Michael N. Molla,Charles R. Cantor,James J. Collins

Bacteria show remarkable adaptability in the face of antibiotic therapeutics. Resistance alleles in drug target-specific sites and general stress responses have been identified in individual end-point isolates1, 2, 3, 4, 5, 6, 7. Less is known, however, about the population dynamics during the development of antibiotic-resistant strains. Here we follow a continuous culture of Escherichia coli facing increasing levels of antibiotic and show that the vast majority of isolates are less resistant than the population as a whole. We find that the few highly resistant mutants improve the survival of the population’s less resistant constituents, in part by producing indole, a signalling molecule generated by actively growing, unstressed cells8. We show, through transcriptional profiling, that indole serves to turn on drug efflux pumps and oxidative-stress protective mechanisms. The indole production comes at a fitness cost to the highly resistant isolates, and whole-genome sequencing reveals that this bacterial altruism is made possible by drug-resistance mutations unrelated to indole production. This work establishes a population-based resistance mechanism constituting a form of kin selection9 whereby a small number of resistant mutants can, at some cost to themselves, provide protection to other, more vulnerable, cells, enhancing the survival capacity of the overall population in stressful environments.

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