近日,，國際著名雜志《自然—遺傳學》Nature Genetics在線刊登了國外研究人員的最新研究成果“Evolutionary paths to antibiotic resistance under dynamically sustained drug selection,。”,，大腸桿菌在抗生素治療過程中獲得了藥物抗性,。研究人員對抗藥性獲得過程的大腸桿菌菌株進行了全基因組測序,，這些實驗是在一種新開發(fā)的實驗室微生物培養(yǎng)設備中進行的,，可實時監(jiān)測細菌種群內藥物抗性的基因組演變,。
Roy Kishony和同事研制出一種名為“morbidostat”的設備,，可在延長時間內自動進化實驗,。通過監(jiān)測細菌生長并調整藥物濃度以提供一種恒定選擇壓力，morbidostat提供了一種更真實的抗性演變實驗室模型,。利用這種morbidostat,，在所選擇的幾個單一藥物之一中,，研究人員檢測了大腸桿菌藥物抗性的演化過程。他們測出了最初對藥物敏感的大腸桿菌的全基因組序列,，以及在25天的藥物使用過程中所分離出這種細菌的全基因組序列,。他們鑒別出賦予變異的新藥物抗性，同時洞察到抗性演化過程中的變異順序和通道,。（生物谷Bioon.com）
doi:10.1038/ng.1034
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Evolutionary paths to antibiotic resistance under dynamically sustained drug selection
Erdal Toprak, Adrian Veres, Jean-Baptiste Michel, Remy Chait, Daniel L Hartl & Roy Kishony
Antibiotic resistance can evolve through the sequential accumulation of multiple mutations1. To study such gradual evolution, we developed a selection device, the 'morbidostat', that continuously monitors bacterial growth and dynamically regulates drug concentrations, such that the evolving population is constantly challenged2, 3, 4, 5. We analyzed the evolution of resistance in Escherichia coli under selection with single drugs, including chloramphenicol, doxycycline and trimethoprim. Over a period of ~20 days, resistance levels increased dramatically, with parallel populations showing similar phenotypic trajectories. Whole-genome sequencing of the evolved strains identified mutations both specific to resistance to a particular drug and shared in resistance to multiple drugs. Chloramphenicol and doxycycline resistance evolved smoothly through diverse combinations of mutations in genes involved in translation, transcription and transport3. In contrast, trimethoprim resistance evolved in a stepwise manner1, 6, through mutations restricted to the gene encoding the enzyme dihydrofolate reductase (DHFR)7, 8. Sequencing of DHFR over the time course of the experiment showed that parallel populations evolved similar mutations and acquired them in a similar order9.
