Discovering novel antibiotics from Streptomyces

从链霉菌中发现新型抗生素

• 批准号: 1654308
• 金额: --
• 依托单位: University of East Anglia
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-1654308
• 关键词: Discovering; novel; antibiotics; Streptomyces

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.

来自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年代以来没有发现新的抗生素。英国首相大卫卡梅隆最近承认，新抗生素的短缺有可能使药物回到黑暗时代，寻找新的抗生素现在是全球健康的优先事项。在过去的六年里，我们一直在寻找新的产抗生素的细菌菌株在真菌生长（切叶）蚂蚁的巢穴中，这些蚂蚁生活在南美洲和中美洲。这是一个以前从未探索过的环境利基，它为发现新菌株和抗生素提供了良好的前景。蚂蚁割下树叶来喂养一种共生真菌，它们把这种真菌作为食物来种植，它们在自己的身体上种植能产生寄生虫的细菌，以保护自己和真菌免受感染。该团队已经分离出超过400种产益生菌的细菌菌株，并开始对其中一些菌株进行详细研究。其中一个菌株是一种新的链霉菌，它能产生至少两种具有新型化学支架的新的NP。对该菌株的完整基因组序列的分析表明，它产生了几种新的NP。在该项目中，成功的申请人将使用基因组分析，活性导向分馏和天然产物化学的组合来鉴定由该链霉菌菌株产生的新型NP，并鉴定这些化合物中每一种的生物合成途径和编码基因簇。新型纳米颗粒将针对多重耐药细菌和真菌进行筛选，以确定可能用于人类医学的先导化合物。

项目成果

Formicamycins, antibacterial polyketides produced by Streptomyces formicae isolated from African Tetraponera plant-ants.

• DOI: 10.1039/c6sc04265a
• 发表时间: 2017-04-01
• 期刊: Chemical science
• 影响因子: 8.4
• 作者: Qin Z;Munnoch JT;Devine R;Holmes NA;Seipke RF;Wilkinson KA;Wilkinson B;Hutchings MI
• 通讯作者: Hutchings MI