Role of Aif1 in regulation of cell death under environmental stress in <i>Candida albicans</i>

Ma, Feiyang; Zhang, Yueqi; Wang, Yuzhou; Wan, Yajuan; Miao, Yun-Heng; Ma, Tianyu; Yu, Qilin; Li, Mingchun

doi:10.1002/yea.3167

Cited by 15 publications

(16 citation statements)

References 33 publications

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“…Cell wall stressors like caspofungin induce an oxidative burst in fungi, including C. albicans (48,49). 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.…”

Section: Discussionsupporting

confidence: 51%

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: 51%

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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“…All of these genes, except for rlm1, ald4, and tdh3 [isoform A], are related to processes of programmed cell death, as SIN3, that is involved in the regulation of mitophagy receptor protein Atg32 in yeast (Aihara et al, 2014). ATG8 is an autophagic protein that plays a key role in autophagosome formation (Dufresne et al, 1998;Nadal and Gold, 2010;Khan et al, 2012); mca1 plays a dual role in the induction of programmed cell death and intracellular protein quality control on exposure to stress conditions (Mukherjee et al, 2017); aif1 is a conserved flavoprotein that causes chromatin condensation and DNA fragmentation, two hallmarks of apoptosis (Susin et al, 1999;Cande et al, 2004;Elguindy and Nakamaru-Ogiso, 2015;Ma et al, 2016); NUC1 causes apoptosis in yeast without the involvement of metacaspase or of apoptosisinducing factor (Büttner et al, 2007); TOR kinase controls the initiation of autophagy, which results in the development of a single membrane structure known as the phagophore (Yorimitsu et al, 2007;Aguilar et al, 2017;Romero-Aguilar et al, 2020).…”

Section: Gene Expression Analysismentioning

confidence: 99%

Identifying Genes Devoted to the Cell Death Process in the Gene Regulatory Network of Ustilago maydis

et al. 2021

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Cell death is a process that can be divided into three morphological patterns: apoptosis, autophagy and necrosis. In fungi, cell death is induced in response to intracellular and extracellular perturbations, such as plant defense molecules, toxins and fungicides, among others. Ustilago maydis is a dimorphic fungus used as a model for pathogenic fungi of animals, including humans, and plants. Here, we reconstructed the transcriptional regulatory network of U. maydis, through homology inferences by using as templates the well-known gene regulatory networks (GRNs) of Saccharomyces cerevisiae, Aspergillus nidulans and Neurospora crassa. Based on this GRN, we identified transcription factors (TFs) as hubs and functional modules and calculated diverse topological metrics. In addition, we analyzed exhaustively the module related to cell death, with 60 TFs and 108 genes, where diverse cell proliferation, mating-type switching and meiosis, among other functions, were identified. To determine the role of some of these genes, we selected a set of 11 genes for expression analysis by qRT-PCR (sin3, rlm1, aif1, tdh3 [isoform A], tdh3 [isoform B], ald4, mca1, nuc1, tor1, ras1, and atg8) whose homologues in other fungi have been described as central in cell death. These genes were identified as downregulated at 72 h, in agreement with the beginning of the cell death process. Our results can serve as the basis for the study of transcriptional regulation, not only of the cell death process but also of all the cellular processes of U. maydis.

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“…Of note, increased caspase activity has been observed in relation to induction of apoptosis in C. albicans exposed to other stimuli, for instance the quorum sensing molecule farnesol [ 98 , 99 ], the plant-derived macrocyclic bisbibenzyl plagiochin E [ 96 ] or silibinin [ 100 ]. In contrast, cell death resulting from caspofungin is executed through a Mca1-independent manner but instead requires Aif1 [ 94 , 101 ].…”

Section: Regulated Cell Death In Fungimentioning

confidence: 99%

Regulated Cell Death as a Therapeutic Target for Novel Antifungal Peptides and Biologics

Yeaman

Büttner

Thevissen

2018

Oxidative Medicine and Cellular Longevity

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The rise of microbial pathogens refractory to conventional antibiotics represents one of the most urgent and global public health concerns for the 21st century. Emergence of Candida auris isolates and the persistence of invasive mold infections that resist existing treatment and cause severe illness has underscored the threat of drug-resistant fungal infections. To meet these growing challenges, mechanistically novel agents and strategies are needed that surpass the conventional fungistatic or fungicidal drug actions. Host defense peptides have long been misunderstood as indiscriminant membrane detergents. However, evidence gathered over the past decade clearly points to their sophisticated and selective mechanisms of action, including exploiting regulated cell death pathways of their target pathogens. Such peptides perturb transmembrane potential and mitochondrial energetics, inducing phosphatidylserine accessibility and metacaspase activation in fungi. These mechanisms are often multimodal, affording target pathogens fewer resistance options as compared to traditional small molecule drugs. Here, recent advances in the field are examined regarding regulated cell death subroutines as potential therapeutic targets for innovative anti-infective peptides against pathogenic fungi. Furthering knowledge of protective host defense peptide interactions with target pathogens is key to advancing and applying novel prophylactic and therapeutic countermeasures to fungal resistance and pathogenesis.

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Role of Aif1 in regulation of cell death under environmental stress in Candida albicans

Cited by 15 publications

References 33 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

Identifying Genes Devoted to the Cell Death Process in the Gene Regulatory Network of Ustilago maydis

Regulated Cell Death as a Therapeutic Target for Novel Antifungal Peptides and Biologics

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