Centre for Genomic Regulation, The Barcelona Institute of Science and Technology, Barcelona, Spain.
Universitat Pompeu Fabra, Barcelona, Spain.
Curr Top Microbiol Immunol. 2019;422:193-235. doi: 10.1007/82_2018_122.
Infections caused by opportunistic human fungal pathogens are a source of increasing medical concern, due to their growing incidence, the emergence of novel pathogenic species, and the lack of effective diagnostics tools. Fungal pathogens are phylogenetically diverse, and their virulence mechanisms can differ widely across species. Despite extensive efforts, the molecular bases of virulence in pathogenic fungi and their interactions with the human host remain poorly understood for most species. In this context, next-generation sequencing approaches hold the promise of helping to close this knowledge gap. In particular, high-throughput transcriptome sequencing (RNA-Seq) enables monitoring the transcriptional profile of both host and microbes to elucidate their interactions and discover molecular mechanisms of virulence and host defense. Here, we provide an overview of transcriptome sequencing techniques and approaches, and survey their application in studying the interplay between humans and fungal pathogens. Finally, we discuss novel RNA-Seq approaches in studying host-pathogen interactions and their potential role in advancing the clinical diagnostics of fungal infections.
机会性人类真菌病原体引起的感染是日益引起医学关注的一个来源,这是由于它们的发病率不断上升、新的致病物种的出现以及缺乏有效的诊断工具。真菌病原体在系统发育上具有多样性,其毒力机制在不同物种之间可能有很大差异。尽管进行了广泛的努力,但对于大多数物种来说,致病真菌的毒力的分子基础及其与人类宿主的相互作用仍然知之甚少。在这种情况下,下一代测序方法有望帮助缩小这一知识差距。特别是,高通量转录组测序(RNA-Seq)能够监测宿主和微生物的转录谱,以阐明它们的相互作用,并发现毒力和宿主防御的分子机制。在这里,我们提供了转录组测序技术和方法的概述,并调查了它们在研究人类和真菌病原体相互作用中的应用。最后,我们讨论了在研究宿主-病原体相互作用中新型 RNA-Seq 方法及其在推进真菌感染的临床诊断中的潜在作用。