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猪蛋白 1 调控新兴真菌病原体耳念珠菌的应激耐受和毒力。

Hog1 Regulates Stress Tolerance and Virulence in the Emerging Fungal Pathogen Candida auris.

机构信息

Institute for Cell and Molecular Biosciences, Faculty of Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom

Institute for Cell and Molecular Biosciences, Faculty of Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.

出版信息

mSphere. 2018 Oct 24;3(5):e00506-18. doi: 10.1128/mSphere.00506-18.

Abstract

has recently emerged as an important, multidrug-resistant fungal pathogen of humans. Comparative studies indicate that despite high levels of genetic divergence, is as virulent as the most pathogenic member of the genus, However, key virulence attributes of , such as morphogenetic switching, are not utilized by , indicating that this emerging pathogen employs alternative strategies to infect and colonize the host. An important trait required for the pathogenicity of many fungal pathogens is the ability to adapt to host-imposed stresses encountered during infection. Here, we investigated the relative resistance of and other pathogenic species to physiologically relevant stresses and explored the role of the evolutionarily conserved Hog1 stress-activated protein kinase (SAPK) in promoting stress resistance and virulence. In comparison to , is relatively resistant to hydrogen peroxide, cationic stress, and cell-wall-damaging agents. However, in contrast to other species examined, was unable to grow in an anaerobic environment and was acutely sensitive to organic oxidative-stress-inducing agents. An analysis of Δ cells revealed multiple roles for this SAPK in stress resistance, cell morphology, aggregation, and virulence. These data demonstrate that has a unique stress resistance profile compared to those of other pathogenic species and that the Hog1 SAPK has pleiotropic roles that promote the virulence of this emerging pathogen. The rapid global emergence and resistance of to current antifungal drugs highlight the importance of understanding the virulence traits exploited by this human fungal pathogen to cause disease. Here, we characterize the stress resistance profile of and the role of the Hog1 stress-activated protein kinase (SAPK) in stress resistance and virulence. Our findings that is acutely sensitive to certain stresses may facilitate control measures to prevent persistent colonization in hospital settings. Furthermore, our observation that the Hog1 SAPK promotes virulence akin to that reported for many other pathogenic fungi indicates that antifungals targeting Hog1 signaling would be broad acting and effective, even on emerging drug-resistant pathogens.

摘要

已经成为一种重要的、多药耐药的人类真菌病原体。比较研究表明,尽管存在高度的遗传分化,但它与属中最具致病性的成员一样具有毒力。然而,的关键毒力属性,如形态发生转换,并没有被利用,这表明这种新兴的病原体采用了替代策略来感染和定植宿主。许多真菌病原体致病性所必需的一个重要特征是能够适应感染过程中宿主施加的应激。在这里,我们研究了和其他致病性物种对生理相关应激的相对抗性,并探讨了进化上保守的 Hog1 应激激活蛋白激酶(SAPK)在促进应激抗性和毒力中的作用。与相比,对过氧化氢、阳离子应激和细胞壁破坏剂具有相对抗性。然而,与所检查的其他物种相反,无法在厌氧环境中生长,并且对有机氧化应激诱导剂非常敏感。对Δ细胞的分析揭示了该 SAPK 在应激抗性、细胞形态、聚集和毒力方面的多种作用。这些数据表明,与其他致病性物种相比,具有独特的应激抗性谱,并且 Hog1 SAPK 具有促进这种新兴病原体毒力的多效性作用。的快速全球出现和对当前抗真菌药物的耐药性突出了了解这种人类真菌病原体利用的毒力特征以引起疾病的重要性。在这里,我们描述了的应激抗性谱和 Hog1 应激激活蛋白激酶(SAPK)在应激抗性和毒力中的作用。我们发现对某些应激的急性敏感性可能有助于采取控制措施,以防止在医院环境中持续定植。此外,我们观察到 Hog1 SAPK 促进类似于许多其他致病性真菌报道的毒力表明,针对 Hog1 信号的抗真菌药物将具有广泛的作用和有效性,即使是针对新兴的耐药病原体也是如此。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d2d3/6200985/a5f15500d45c/sph0051826640001.jpg

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