A new antibiotic kills pathogens without detectable resistance

摘要

Antibiotic resistance is spreading faster than the introduction of new compounds into clinical practice, causing a public health crisis. Most antibiotics were produced by screening soil microorganisms, but this limited resource of cultivable bacteria was overmined by the 1960s. Synthetic approaches to produce antibiotics have been unable to replace this platform. Uncultured bacteria make up approximately 99 % of all species in external environments, and are an untapped source of new antibiotics. We developed several methods to grow uncultured organisms by cultivation in situ or by using specific growth factors. Here we report a new antibiotic that we term teixobactin, discovered in a screen of uncultured bacteria. Teixobactin inhibits cell wall synthesis by binding to a highly conserved motif of lipid Ⅱ (precursor of peptidoglycan) and lipid Ⅲ (precursor of cell wall teichoic acid). We did not obtain any mutants of Staphylococcus aureus or Mycobacterium tuberculosis resistant to teixobactin. The properties of this compound suggest a path towards developing antibiotics that are likely to avoid development of resistance.%临床应用中的大部分抗生素都是通过筛选可培养的土壤微生物发现的，这是一个在很大程度上已经耗尽、没有通过合成方法得到充分替代的资源。因此，对于抗生素抗药性之扩散的担心普遍存在。这篇论文带来了一些好消息: 对包括"金黄色葡萄球菌"在内的一系列细菌病原体有活性、并且明显不受抗药性的演变影响的一种新的抗生素已被分离和表征。Kim Lewis及同事利用最近建立的一个系统对以前未培养的土壞细菌进行原位培养，识别出一种β-变形杆菌"Eleftheria terrae sp.",它能产生一种他们称之为"teixobactin"的酯肽。Teixobactin在活体中有活性，分别以细菌细胞壁中两大主要成分"肽聚糖"和"磷壁酸"其中之一的生物合成通道中的前体为作用目标。寻找对teixobactin有抵抗力的突变体的筛选工作结果是阴性的，这也许是由这种新颖的双目标作用机制造成的。