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用于揭示生物膜形成和耐药性的转录组学和基因组学方法——最新进展

Transcriptomic and Genomic Approaches for Unravelling Biofilm Formation and Drug Resistance-An Update.

作者信息

Chong Pei Pei, Chin Voon Kin, Wong Won Fen, Madhavan Priya, Yong Voon Chen, Looi Chung Yeng

机构信息

School of Biosciences, Faculty of Health and Medical Sciences, Taylor's University Malaysia, Subang Jaya, 47500 Selangor, Malaysia.

Department of Microbiology, Faculty of Medicine, University Malaya, 50603 Kuala Lumpur, Malaysia.

出版信息

Genes (Basel). 2018 Nov 7;9(11):540. doi: 10.3390/genes9110540.

Abstract

is an opportunistic fungal pathogen, which causes a plethora of superficial, as well as invasive, infections in humans. The ability of this fungus in switching from commensalism to active infection is attributed to its many virulence traits. Biofilm formation is a key process, which allows the fungus to adhere to and proliferate on medically implanted devices as well as host tissue and cause serious life-threatening infections. Biofilms are complex communities of filamentous and yeast cells surrounded by an extracellular matrix that confers an enhanced degree of resistance to antifungal drugs. Moreover, the extensive plasticity of the genome has given this versatile fungus the added advantage of microevolution and adaptation to thrive within the unique environmental niches within the host. To combat these challenges in dealing with infections, it is imperative that we target specifically the molecular pathways involved in biofilm formation as well as drug resistance. With the advent of the -omics era and whole genome sequencing platforms, novel pathways and genes involved in the pathogenesis of the fungus have been unraveled. Researchers have used a myriad of strategies including transcriptome analysis for cells grown in different environments, whole genome sequencing of different strains, functional genomics approaches to identify critical regulatory genes, as well as comparative genomics analysis between and its closely related, much less virulent relative, , in the quest to increase our understanding of the mechanisms underlying the success of as a major fungal pathogen. This review attempts to summarize the most recent advancements in the field of biofilm and antifungal resistance research and offers suggestions for future directions in therapeutics development.

摘要

是一种机会性真菌病原体,可导致人类多种浅表和侵袭性感染。这种真菌从共生状态转变为主动感染的能力归因于其许多毒力特征。生物膜形成是一个关键过程,它使真菌能够附着在医疗植入设备以及宿主组织上并增殖,从而引发严重的危及生命的感染。生物膜是由丝状和酵母细胞组成的复杂群落,被细胞外基质包围,这种基质赋予了对抗真菌药物更高程度的抗性。此外,基因组的广泛可塑性赋予了这种多功能真菌微进化和适应在宿主体内独特生态位中茁壮成长的额外优势。为了应对这些感染方面的挑战,我们必须专门针对参与生物膜形成以及耐药性的分子途径。随着组学时代和全基因组测序平台的出现,与该真菌发病机制相关的新途径和基因已被揭示。研究人员使用了多种策略,包括对在不同环境中生长的细胞进行转录组分析、对不同菌株进行全基因组测序、采用功能基因组学方法来鉴定关键调控基因,以及在该真菌与其密切相关但毒力低得多的相对菌株之间进行比较基因组学分析,以增进我们对该真菌作为主要真菌病原体成功机制的理解。本综述试图总结生物膜和抗真菌耐药性研究领域的最新进展,并为治疗学发展的未来方向提供建议。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3bca/6266447/d47bad37e7cb/genes-09-00540-g001.jpg

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