Endoplasmic reticulum-derived reactive oxygen species (ROS) is involved in toxicity of cell wall stress to Candida albicans

Yu, Qilin; Zhang, Bing; Lǐ, Jiànróng; Zhang, Biao; Wang, Honggang; Li, Mingchun

doi:10.1016/j.freeradbiomed.2016.09.014

Cited by 60 publications

(54 citation statements)

References 57 publications

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“…Our data not only showed a caspofungin-induced upregulation of transcripts related to this pathway but also induced an increase in ROS production in both strains of C. auris. Similar observations were reported for C. albicans, of which caspofungin-induced cell wall stress increased ROS generation (50). Caspofungin also affects the oxidative stress response in A. fumigatus, of which many mRNAs related to this pathway are upregulated in the presence of the antifungal (51).…”

Section: Discussionsupporting

confidence: 75%

Integrated transcriptional analysis of the cellular and extracellular vesicle RNA content of Candida auris in response to caspofungin

Miranda

Amatuzzi

Martins

et al. 2020

Preprint

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Candida auris has emerged as a serious worldwide threat by causing invasive infections in humans that are frequently resistant to one or more conventional antifungal medications, resulting in high mortality rates. Against this backdrop, health warnings around the world have focused efforts on understanding C. auris fungal biology and effective treatment approaches to combat this fungus. To date, there is little information about C. auris gene expression regulation in response to antifungal treatment. Our integrated analyses focused on the comparative transcriptomics of C. auris in the presence and absence of caspofungin as well as a detailed analysis of the yeast’s extracellular vesicle (EV)-RNA composition. The results showed that genes coding oxidative stress response, ribosomal proteins, cell wall, and cell cycle were significantly upregulated in the presence of caspofungin, whereas transcriptional regulators and proteins related to the nucleus were downregulated. The mRNAs in the EVs were associated with stress responses induced by caspofungin and the ncRNA content of the EVs shifted during caspofungin treatment. Altogether, the results provide further insights into the fungal response to caspofungin and demonstrate that analyses of C. auris growth under antifungal stress can elucidate resistance and survival mechanisms of this fungus in response to medical therapy.

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Section: Discussionsupporting

confidence: 75%

Integrated transcriptional analysis of the cellular and extracellular vesicle RNA content of Candida auris in response to caspofungin

Miranda

Amatuzzi

Martins

et al. 2020

Preprint

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“…Cap1p is a bZIP transcription factor that controls antioxidant gene expression and HOG1 encodes a transcription factor that activates a MAP-kinase cascade to result in resistance to oxidative stresses [91,92]. Overaccumulation of reactive oxidative species (ROS) compromises cell wall integrity and affects the maturation of the proteins in the ER, impacting C. albicans virulence [95,96]. Furthermore, ER functioning requires tight regulation of ER lumenal calcium levels, which is maintained by Spf1p, a key P-type ATPase [97].…”

Section: Protein Folding and Maturationmentioning

confidence: 99%

The Role of Secretory Pathways in Candida albicans Pathogenesis

Rollenhagen

Mamtani

et al. 2020

JoF

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Candida albicans is a fungus that is a commensal organism and a member of the normal human microbiota. It has the ability to transition into an opportunistic invasive pathogen. Attributes that support pathogenesis include secretion of virulence-associated proteins, hyphal formation, and biofilm formation. These processes are supported by secretion, as defined in the broad context of membrane trafficking. In this review, we examine the role of secretory pathways in Candida virulence, with a focus on the model opportunistic fungal pathogen, Candida albicans.

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“…We could not exclude the possibility that part of the ROS was derived from the disturbed ER. Recently, we have reported that ER stress caused by cell wall damage may induce Ero-dependent production of ROS [32]. Herein, we observed morphological change of the ER in the mutant, implying that ER function might also be impaired by deletion of ARF1, which might further result in ER stress and consequent ROS production.…”

Section: Discussionmentioning

confidence: 68%

“…Intracellular ROS was detected using the oxidant‐sensitive agent 2′,7′‐dichlorofluorescein diacetate (Sigma‐Aldrich, St Louis, MO, USA) . This was added (at final concentration 10 μg·mL −1 ) to the prepared cell culture for staining (30 °C, 40 min).…”

Section: Methodsmentioning

confidence: 99%

Arf1 regulates the ER–mitochondria encounter structure (ERMES) in a reactive oxygen species‐dependent manner

Zhang

Huo

et al. 2018

The FEBS Journal

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The Arf family of small GTP-binding and -hydrolyzing proteins are some of the most important intracellular regulators of membrane dynamics. In this study, we identified the Golgi-localized Arf family G protein Arf1 in Candida albicans and confirmed its conserved function in regulating the secretory pathway. Interestingly, deletion of ARF1 resulted in intracellular reactive oxygen species (ROS) accumulation, and induced formation of the endoplasmic reticulum (ER)-mitochondria encounter structure (ERMES). Moreover, N-acetylcysteine-mediated ROS scavenging in the arf1Δ/Δ strain attenuated ERMES formation, indicating that intracellular ROS accumulation resulting from ARF1 deletion facilitated ERMES formation. In addition, Arf1 regulated many key physiological processes in C. albicans, including cell cycle progression, morphogenesis and virulence. This study uncovers a role for Arf family G proteins in regulating ERMES formation and sheds new light on the crucial contribution of ROS to membrane dynamics.

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Endoplasmic reticulum-derived reactive oxygen species (ROS) is involved in toxicity of cell wall stress to Candida albicans

Cited by 60 publications

References 57 publications

Integrated transcriptional analysis of the cellular and extracellular vesicle RNA content of Candida auris in response to caspofungin

Integrated transcriptional analysis of the cellular and extracellular vesicle RNA content of Candida auris in response to caspofungin

The Role of Secretory Pathways in Candida albicans Pathogenesis

Arf1 regulates the ER–mitochondria encounter structure (ERMES) in a reactive oxygen species‐dependent manner

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