Discovering novel antibiotics from Streptomyces

链霉菌及其近亲的天然产物(NPs)占目前人类医学中使用的抗生素的三分之二，但自20世纪80年代以来就没有发现过新的抗生素类别。英国首相戴维·卡梅伦最近承认，新抗生素的短缺可能会将医学带回黑暗时代，寻找新的抗生素现在是全球健康的首要任务。在过去的六年里，我们一直在南美洲和中美洲的真菌(切叶)蚂蚁的巢穴中寻找新的抗生素产生菌株。这是一个以前从未被探索过的环境利基，它为发现新的菌株和抗生素提供了良好的前景。蚂蚁剪下叶子，喂食一种共生真菌，它们种植这种真菌作为食物，并在自己的身体上培养产生抗生素的细菌，以保护自己和真菌免受感染。该团队已经分离出400株产生抗生素的细菌，并开始对其中一些菌株进行详细的特征分析。其中一个菌株是链霉菌的一种新物种，它至少产生两类新的NP，具有新颖的化学支架。对这种菌株的完整基因组序列的分析表明，它制造了几个更新的NPs。在这个项目中，成功的申请者将结合基因组分析、活性指导分离和天然产物化学来表征这种链霉菌菌株制造的新型NPs，并确定每种化合物的生物合成途径和编码基因簇。新的纳米粒子将被筛选出来对抗多重耐药细菌和真菌，以识别可能在人类医学中有用的先导化合物。

Natural products (NPs) from Streptomyces bacteria and their close relatives account for two thirds of the antibiotics currently used in human medicine but no new classes of antibiotic have been discovered since the 1980s. The UK Prime Minister David Cameron recently acknowledged that the shortage of new antibiotics threatens to take medicine back to the dark ages and the search for new antibiotics is now a global health priority.For the last six years we have been searching for novel antibiotic-producing strains of bacteria in the nests of fungus growing (leafcutter) ants which live in South and Central America. This is an environmental niche that has not been explored before and it offers good prospects for the discovery of novel strains and antibiotics. The ants cut leaves to feed to a symbiotic fungus which they grow for food and they grow antibiotic-producing bacteria on their bodies to protect themselves and their fungus against infections. The team has isolated > 400 strains of antibiotic-producing bacteria and started to characterise some of these strains in detail. One such strain is a new species of Streptomyces that produces at least two new classes of NP with novel chemical scaffolds. Analysis of the complete genome sequence of this strain suggests it makes several more novel NPs. In this project the successful applicant will use a combination of genome analysis, activity guided fractionation and natural products chemistry to characterise the novel NPs made by this Streptomyces strain and to identify the biosynthetic pathways and encoding gene clusters for each of these compounds. Novel NPs will be screened against multidrug resistant bacteria and fungi to identify lead compounds that may be useful in human medicine.