THE ROLE OF EXTRACELLULAR VESICLES IN REGULATING DIVISION OF LABOUR IN FUNGI

细胞外囊泡在调节真菌分工中的作用

• 批准号: BB/R008485/1
• 负责人: Robin May
• 金额: $ 51.9万
• 依托单位: University of Birmingham
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FR008485%2F1
• 关键词: ROLE; EXTRACELLULAR; VESICLES; REGULATING; DIVISION

Many animal species use teamwork in order to maximize fitness through Division of Labour: for instance, via the allocation of guard duties and food gathering duties to different individuals in social insects. However, a recent and surprising discovery has been that single-celled microbes are also capable of Division of Labour. Moreover, such behaviours often underlie important processes such as antimicrobial resistance in bacteria.We have recently discovered a novel Division of Labour behaviour in the fatal fungal pathogen Cryptococcus gattii. Upon entry into the host, individual fungal cells communicate in order to adopt two different fates: some individuals stop growing and become quiescent "guard cells", which then protect the other "proliferative" individuals from being killed by the host. This enables the fungus to grow rapidly and overwhelm the host; something that neither fungal cell type can achieve alone.The mechanism by which this Division of Labour occurs at the molecular level is completely unknown. However, we have recent data demonstrating that the cell-to-cell communication it entails is carried out by extracellular vesicles, which act as long-distance "carrier pigeons" to enable fungal cells to coordinate their behaviour over large distances. The aim of this proposal is therefore to dissect, for the first time, the nature of this novel virulence mechanism by:1. discovering how extracellular vesicles coordinate fungal behaviour2. characterizing the contents of these vesicles3. identifying how these vesicles are transported between fungi and their surrounding host cells4. revealing how host cells respond to this fungal manipulation.In doing so, we aim to reveal a completely new type of pathogenesis mechanism in an important human and animal disease. In addition, since i) Division of Labour mechanisms operate in a diverse range of microbes, and ii) extracellular vesicles are known to be shed by a large number of bacterial and fungal species, it is possible that the processes we will unveil within this project may provide a broad paradigm for understanding Division of Labour across the full breadth of microbiology.

许多动物物种利用团队合作，通过分工来最大限度地提高适应性：例如，通过将守卫职责和食物采集职责分配给社会性昆虫的不同个体。然而，最近的一个令人惊讶的发现是单细胞微生物也能够进行劳动分工。此外，此类行为通常是细菌耐药性等重要过程的基础。我们最近在致命的真菌病原体格特隐球菌中发现了一种新的分工行为。进入宿主后，各个真菌细胞进行通信，以采取两种不同的命运：一些个体停止生长并成为静止的“保卫细胞”，然后保护其他“增殖”个体不被宿主杀死。这使得真菌能够快速生长并压垮宿主；两种真菌细胞类型都无法单独实现这一目标。这种分工在分子水平上发生的机制完全未知。然而，我们最近的数据表明，它所需要的细胞间通讯是由细胞外囊泡进行的，细胞外囊泡充当长距离的“信鸽”，使真菌细胞能够在长距离内协调其行为。因此，该提案的目的是通过以下方式首次剖析这种新型毒力机制的性质：1。发现细胞外囊泡如何协调真菌行为2。表征这些囊泡的内容物3。确定这些囊泡如何在真菌与其周围宿主细胞之间运输4。揭示宿主细胞如何响应这种真菌操作。在此过程中，我们的目标是揭示一种重要的人类和动物疾病的全新发病机制。此外，由于 i) 劳动分工机制在多种微生物中发挥作用，ii) 众所周知，细胞外囊泡是由大量细菌和真菌物种脱落的，因此我们将在本项目中揭示的过程可能会为理解整个微生物学领域的劳动分工提供一个广泛的范式。

项目成果

Pyrifenox, an ergosterol inhibitor, differentially affects Cryptococcus neoformans and Cryptococcus gattii.

Pyrifenox 是一种麦角甾醇抑制剂，对新型隐球菌和格特隐球菌有不同的影响。

• DOI: 10.1093/mmy/myz132
• 发表时间: 2020
• 期刊: Medical mycology
• 影响因子: 2.9
• 作者: Silva VKA

Pathogen-derived extracellular vesicles mediate virulence in the fatal human pathogen Cryptococcus gattii.

• DOI: 10.1038/s41467-018-03991-6
• 发表时间: 2018-04-19
• 期刊: Nature communications
• 影响因子: 16.6
• 作者: Bielska E;Sisquella MA;Aldeieg M;Birch C;O'Donoghue EJ;May RC
• 通讯作者: May RC

Application of High-Field Asymmetric Waveform Ion Mobility Separation to LESA Mass Spectrometry of Bacteria.

高场不对称波形离子淌度分离在细菌 LESA 质谱分析中的应用。

• DOI: 10.1021/acs.analchem.9b00307
• 发表时间: 2019
• 期刊: Analytical chemistry
• 影响因子: 7.4
• 作者: Kocurek KI

An in vitro method for inducing titan cells reveals novel features of yeast-to-titan switching in the human fungal pathogen Cryptococcus gattii.

• DOI: 10.1371/journal.ppat.1010321
• 发表时间: 2022-08
• 期刊: PLoS pathogens
• 影响因子: 6.7