Establishment of an innovative co-cultivation platform for high-throughput identification of antimicrobial compounds

建立用于高通量鉴定抗菌化合物的创新共培养平台

• 批准号: 404295023
• 负责人: Professorin Dr.-Ing. Vera Meyer
• 金额: --
• 依托单位: Fachgebiet Angewandte und Molekulare Mikrobiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2023-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/404295023?language=en
• 关键词: Establishment; innovative; co; cultivation; platform

In the alarming context of the recurrent emergence of multi-resistant pathogenic bacteria and fungi, uncharted territories in microbiological research and bioprocess engineering must be explored. The prevailing method of growing pure (axenic) culture of microorganisms, as of today still the common praxis since its introduction by Robert Koch in the late XIX century, must be implemented with innovative technologies for the establishment of mixed-species cultures.The intensive investigation during the last two decades of genome sequence data from filamentous fungi and bacteria in the quest for new antibiotic and antimycotic genes led to the unexpected observation that in most sequenced species about 30-50 gene clusters are present, which similarly to penicillin from the fungus Penicillium chrysogenum could set in motion a new era in medicine. The surprise: most of the discovered gene clusters are inactive and do not lead to the production of a bioactive substance when bacteria and fungi are cultivated in axenic cultures. This potential cannot thus be fully exploited with methodologies used in classical microbiological studies and is one of the pivotal reasons why since about 20 years no new class of antibiotic could be identified from microbial pure cultures. The low-hanging fruits have been harvested and the end of the era of single-species cultivations muss be ushered. Scientific breakthroughs can be achieved by considering the metabolic activities of mixed-species cultures including the analysis of the metabolism of yetuncultivable microorganisms that are not viable as pure cultures. This analysis must occur at the systems biology level (transcriptomic, proteomic and metabolomics) to allow for a holistic, from genotype-to-chemotype understanding of microbial metabolism as well as to provide new technical approaches for a controlled and reproducible cultivation methodology to ensure the generation of reliable and robust data.The research concept of the present proposal meets the requirements for the development of new co-cultivation approaches and methodologies for the stable in vitro cultivation of natural, complex mixed-species populations of microorganisms for the discovery of hitherto unknown substances and substance classes for current societal and medical challenges, their bioactivity testing as antibacterials and antifungals as well as the correlation with the corresponding genetic clusters.

在令人震惊的背景下，反复出现的多重耐药致病细菌和真菌，在微生物学研究和生物工艺工程的未知领域必须探索。自十九世纪后期罗伯特·科赫（Robert Koch）引入以来，培养微生物纯（无菌）培养物的流行方法至今仍然是普遍的实践，必须采用创新技术，以建立混合-在过去的二十年里，为了寻找新的抗生素和抗真菌基因，对丝状真菌和细菌的基因组序列数据进行了深入的研究，在大多数测序物种中存在约30-50个基因簇的意想不到的观察结果，这类似于来自真菌产黄青霉的青霉素，可能会开启医学的新时代。惊喜：大多数发现的基因簇是无活性的，并且当细菌和真菌在无菌培养物中培养时不会导致生物活性物质的产生。因此，这种潜力不能用经典微生物学研究中使用的方法充分利用，这是大约20年来无法从微生物纯培养物中鉴定出新类别抗生素的关键原因之一。低垂的果实已经收获，单一物种栽培时代的结束必须到来。通过考虑混合物种培养物的代谢活动，包括分析纯培养物不能存活的不可培养微生物的代谢，可以实现科学突破。这种分析必须在系统生物学水平上进行（转录组学，蛋白质组学和代谢组学），以允许一个整体，从基因型到化学型的微生物代谢的理解，以及提供新的技术方法，为控制和可重复的培养方法，以确保产生可靠和强大的数据。本提案的研究概念符合新的合作开发的要求，培养途径和方法，用于在体外稳定培养天然的、复杂的混合物种微生物种群，以发现迄今未知的物质和物质类别，以应对当前的社会和医学挑战，进行其作为抗菌剂和抗真菌剂的生物活性测试，以及与相应的遗传簇的相关性。