New Tuberculosis Antibiotics from Filamentous Fungi

来自丝状真菌的新型结核病抗生素

• 批准号: 7611508
• 负责人: Cedric Pearce
• 金额: $ 13.6万
• 依托单位: MYCOSYNTHETIX, INC.
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-02-13 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7611508
• 关键词: Agriculture; Aliquot; Anti-Bacterial Agents; Antibiotics; Antitubercular Agents; Bacteria; Chemicals; Chemistry; Collaborations; Collection; Column Chromatography; Communities; Complex; Culture Techniques; Data; Development; Disease; Drug Resistant Tuberculosis; Evaluation; Extreme drug resistant tuberculosis; Fermentation; Fractionation; Goals; Growth; HIV; High Pressure Liquid Chromatography; Illinois; In Vitro; Institutes; Interest Group; Lead; Legal patent; Mammalian Cell; Medicine; Membrane; Methods; Microbiology; Molds; Molecular; Multidrug-Resistant Tuberculosis; Organism; Patients; Peer Review; Pesticides; Pharmaceutical Chemistry; Pharmaceutical Preparations; Phase; Population; Process; Production; Productivity; Publishing; Research; Research Proposals; Review Literature; Sampling; Screening procedure; Small Business Innovation Research Grant; Solvents; Source; Taxonomy; Techniques; Testing; Time; Tuberculosis; Universities; Work; base; combat; fungus; in vivo; innovation; interest; meetings; programs; public health relevance; research study; tuberculosis treatment; web site

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.

描述（由申请人提供）：世界上大约三分之一的人口感染了导致结核病（TB）的细菌;其中十分之一将发展为活动性TB。目前结核病的治疗是复杂和漫长的，涉及抗菌剂的鸡尾酒。合并感染艾滋病毒的患者更容易转化为活动型结核病，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。迫切需要新的药物来防治这种疾病。Mycosynthetix拥有从世界各地收集的约55，000种丝状真菌;这些生物体已被用于发现计划，作为各种疾病的潜在新药来源和农业杀虫剂。在伊利诺伊大学结核病研究所的一项初步研究中，已经对大约12，000个真菌样本进行了抗结核病活性测试;许多真菌已经显示出抑制结核病的生长而不影响哺乳动物细胞。该第I阶段SBIR项目是一项原则证明研究，将调查这些主要培养物并对其进行优先排序。在这项研究中，将使用各种传统和创新的培养技术培养主要真菌，目的是生产高活性的培养物以供进一步评估。此外，涉及使用膜支持物的发酵技术将作为生产含有最小培养基组分的活性提取物的方法进行评价;这可能会简化生产工艺，从而产生廉价且广泛可用的药物。最后，三种最有前途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价的对象。公共卫生关系：结核病感染了大约20亿人;由于治疗方案复杂，艾滋病毒和艾滋病毒药物使其变得更加复杂，以及多重耐药结核病类型（MDR-TB，XDR-TB）的出现，迫切需要新药。在与伊利诺伊大学结核病研究所的合作中，Mycosynthetix已经鉴定了从世界各地收集的丝状真菌，这些丝状真菌可以产生抗结核化合物。该项目证明了这些真菌代谢物可以成为结核病新药的基础。