對抗菌素有抗藥性的細菌菌種的出現,是臨床環境中一個越來越大的威脅,但人們對它們出現的過程卻不是很了解。利用暴露於濃度不斷增大的氟喹諾酮抗菌藥「諾氟沙星」的一個大腸桿菌連續培養物所做實驗表明,少數自然出現的抗藥變體能保護其種群的絕大部分。這些具有高度抗藥性的分離菌種產生信號作用分子「吲哚」,它能激發易感皮膚中的藥物外排泵和其他保護機制。
「超級細菌」基因強悍難治但易防
新型超級細菌抗藥性極強可能全球蔓延
上海藥物研究所啟動抗「超級細菌」藥物研究
超級細菌遭熱炒國內藥企澄清無解藥
超級細菌或激活醫療產業鏈
超級細菌為「耐藥基因」 人類抗生素時代終結?
這種利他行為使較弱的成分能夠存活,並有機會進行有益的突變。對細菌的細胞內通信的使用情況進行更多研究,對於用以控制抗藥性細菌感染的臨床幹預手段的合理設計可能會被證明是有價值的。本期封面上的「紅十字」圖是用數位化手段從大腸桿菌種群的圖像生成的。(生物谷Bioon.com)
生物谷推薦英文摘要:
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.