New Tuberculosis Antibiotics from Filamentous Fungi

描述(由申请人提供)：世界上约三分之一的人口感染了导致结核病的细菌；其中十分之一的人将发展为活动性结核病。目前对结核病的治疗是复杂和漫长的，涉及到抗菌剂的鸡尾酒。合并感染艾滋病毒的患者更容易转变为结核病的活跃形式，治疗每种疾病的药物相互作用很差。耐药结核病已经出现并蔓延；耐多药结核病和广泛耐药结核病极难治愈。迫切需要新药来抗击这种疾病。MyCosynthetix拥有从世界各地收集的大约55,000种丝状真菌；这些生物已被用于发现计划，作为治疗各种疾病的潜在新药和农业杀虫剂的来源。在与伊利诺伊大学结核病研究所的一项初步研究中，对大约12,000个真菌样本进行了抗结核病活性测试；一些真菌被证明在不影响哺乳动物细胞的情况下抑制结核病的生长。第一阶段SBIR项目是一项原则研究的证明，它将调查这些主导文化并确定它们的优先顺序。在这项研究中，铅真菌将使用各种传统和创新的培养技术进行培养，目的是生产出高活性的培养物供进一步评估。此外，涉及使用膜载体的发酵技术将作为一种生产含有最低基质成分的活性提取物的方法进行评估；这可能会简化生产过程，从而产生一种廉价的、因此可广泛获得的药物。最后，这三种最有希望的真菌将成为第二阶段项目中进行的更广泛的化学和药理学评估的对象。与公共卫生相关：结核病感染约20亿人；由于治疗制度复杂，艾滋病毒和艾滋病毒药物使其更加复杂，以及出现耐多药结核病类型(耐多药结核病、广泛耐药结核病)，迫切需要新的药物。在与伊利诺伊大学结核病研究所的合作下，Mycoynthetix鉴定了从世界各地收集的丝状真菌，这些真菌产生抗结核病化合物。该项目证明了这些真菌代谢物可以成为治疗结核病的新药的基础。

DESCRIPTION (provided by applicant): Approximately one third of the world's population is infected with the bacterium which causes tuberculosis (TB); one tenth of these will develop active TB. The current treatment for TB is complex and lengthy involving a cocktail of antibacterial agents. Patients who are co-infected with HIV convert to the active form of TB more readily, with the medicines for each disease interacting poorly. Drug resistant TB has emerged and spread; MDR-TB and XDR-TB are extremely difficult to cure. New medicines are urgently needed to combat this disease. Mycosynthetix owns a collection of approximately 55,000 filamentous fungi which were collected from around the world; these organisms have been used in discovery programs as a source for potential new medicines for a variety of diseases and as agricultural pesticides. In a preliminary study with the Institute for TB Research at the University of Illinois approximately 12,000 fungal samples have been tested for anti TB activity; a number of fungi have been shown to inhibit the growth of TB without effecting mammalian cells. This Phase I SBIR project is a proof of principle study which will investigate these lead cultures and prioritize them. In this study the lead fungi will be cultured using a variety of traditional and innovative culturing techniques with a goal of producing highly active cultures for further evaluation. In addition fermentation techniques involving the use of membrane supports will be evaluated as a method for producing active extracts containing minimal media components; this may introduce the possibility of simplifying the production process resulting in an inexpensive and therefore widely available medicine. Finally the three most promising fungi will be the subjects of a more extensive chemical and pharmacological evaluation to be conducted in a Phase II project. PUBLIC HEALTH RELEVANCE: TB infects approximately 2 billion people; because of complex regimes for treatment, which are made more complicated by HIV and HIV medicines, and the emergence of multiply drug resistant TB types (MDR-TB, XDR-TB) new drugs are urgently needed. In collaboration with the Institute for TB Research at the University of Illinois, Mycosynthetix has identified filamentous fungi collected from around the world which produce anti TB compounds. This project is a proof of concept that these fungal metabolites can form the basis for new medicines for TB.