Teredinibacter turnerae is an intracellular bacterial symbiont in the gills of wood-eating shipworms, where it is proposed to use antibiotics to defend itself and its animal host. Several biosynthetic gene clusters are conserved in T. turnerae and their host shipworms around the world, implying that they encode defensive compounds. Here, we describe turnercyclamycins, lipopeptide antibiotics encoded in the genomes of all sequenced T. turnerae strains. Turnercyclamycins are bactericidal against challenging Gram-negative pathogens, including colistin-resistant Acinetobacter baumannii. Phenotypic screening identified the outer membrane as the likely target. Turnercyclamycins and colistin operate by similar cellular, although not necessarily molecular, mechanisms, but turnercyclamycins kill colistin-resistant A. baumannii, potentially filling an urgent clinical need. Thus, by exploring environments that select for the properties we require, we harvested the fruits of evolution to discover compounds with potential to target unmet health needs. Investigating the symbionts of shipworms is a powerful example of this principle.

Teredinibacter Turnerae是一种存在于食木船蛆鳃中的细胞内细菌共生体，建议使用抗生素来保护自身及其动物宿主。世界各地的T. Turnerae及其宿主船虫中保留了几个生物合成基因簇，这意味着它们编码防御化合物。在这里，我们描述了特纳环霉素，所有已测序的特纳环霉素菌株的基因组中编码的脂肽抗生素。特纳环霉素对具有挑战性的革兰氏阴性病原体具有杀菌作用，包括耐粘菌素的鲍曼不动杆菌。表型筛选将外膜确定为可能的目标。特纳环霉素和粘菌素通过相似的细胞机制（尽管不一定是分子机制）发挥作用，但特纳环霉素可杀死耐粘菌素的鲍曼不动杆菌，可能满足紧急的临床需求。因此，通过探索选择我们所需特性的环境，我们收获了进化的成果，发现了有可能满足未满足的健康需求的化合物。对船蛆共生体的研究就是这一原理的有力例子。