From Genes to Networks: The Regulatory Circuitry Controlling Candida albicans Morphogenesis

Basso, Virginia; d’Enfert, Christophe; Znaidi, Sadri; Bachellier‐Bassi, Sophie

doi:10.1007/82_2018_144

Cited by 35 publications

(48 citation statements)

References 276 publications

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“…For instance, high ATP levels resulting from mitochondrial respiratory activity have been shown to be crucial for C. albicans to switch from yeast cells to mycelium growth [ 20 , 64 , 65 ]. Because this morphogenetic transition is thought to be related to C. albicans virulence [ 66 ], this result shows that mitochondrial respiration can mediate C. albicans virulence by affecting morphogenetic transition. On the other hand, mitochondrial respiration plays an important role in hypoxia signaling and adaptation [ 60 ].…”

Section: Roles Of Mitochondria In Fungal Pathogenicitymentioning

confidence: 99%

Mitochondria-Mediated Azole Drug Resistance and Fungal Pathogenicity: Opportunities for Therapeutic Development

Song

Zhou

Zhang³

et al. 2020

Microorganisms

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In recent years, the role of mitochondria in pathogenic fungi in terms of azole resistance and fungal pathogenicity has been a rapidly developing field. In this review, we describe the molecular mechanisms by which mitochondria are involved in regulating azole resistance and fungal pathogenicity. Mitochondrial function is involved in the regulation of drug efflux pumps at the transcriptional and posttranslational levels. On the one hand, defects in mitochondrial function can serve as the signal leading to activation of calcium signaling and the pleiotropic drug resistance pathway and, therefore, can globally upregulate the expression of drug efflux pump genes, leading to azole drug resistance. On the other hand, mitochondria also contribute to azole resistance through modulation of drug efflux pump localization and activity. Mitochondria further contribute to azole resistance through participating in iron homeostasis and lipid biosynthesis. Additionally, mitochondrial dynamics play an important role in azole resistance. Meanwhile, mitochondrial morphology is important for fungal virulence, playing roles in growth in stressful conditions in a host. Furthermore, there is a close link between mitochondrial respiration and fungal virulence, and mitochondrial respiration plays an important role in morphogenetic transition, hypoxia adaptation, and cell wall biosynthesis. Finally, we discuss the possibility for targeting mitochondrial factors for the development of antifungal therapies.

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Section: Roles Of Mitochondria In Fungal Pathogenicitymentioning

confidence: 99%

Mitochondria-Mediated Azole Drug Resistance and Fungal Pathogenicity: Opportunities for Therapeutic Development

Song

Zhou

Zhang³

et al. 2020

Microorganisms

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“…This scheme is highly simplified: for example, the Mep2 receptor is involved in nitrogen starvation sensing [91], while other stimuli such as alkaline pH or GlcNAc, activate other receptors [103,104]; HGC1 is transcribed by Ume6 during hyphal extension, but initial activation relies on other TFs [97]. More comprehensive descriptions of the various pathways involved in hyphal induction under different conditions and by alternative stimuli can be found in recent reviews [22,105]. In common with the scheme in Figure 1, these parallel pathways (examples of which are shown in red in Figure 2 below) all involve linear transduction of signals from the environment via gene expression regulation to the activation of hyphal effector proteins.…”

Section: Induction Of the Hyphal Morphogenesis Of C Albicans By Ementioning

confidence: 99%

“…Furthermore, some HSGs such as RBT5 can also be expressed in yeast-form cells under certain conditions such as iron starvation [115,116]. Thus, it was suggested that the hypha-specific genes (HSGs) might be more correctly referred to as hypha-associated genes (HAGs) [105]. Nonetheless, we will retain the customary nomenclature here and call these genes HSGs.…”

Section: Induction Of the Hyphal Morphogenesis Of C Albicans By Ementioning

confidence: 99%

Regulation of Candida albicans Hyphal Morphogenesis by Endogenous Signals

Kornitzer

2019

JoF

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Candida albicans is a human commensal fungus that is able to assume several morphologies, including yeast, hyphal, and pseudohyphal. Under a range of conditions, C. albicans performs a regulated switch to the filamentous morphology, characterized by the emergence of a germ tube from the yeast cell, followed by a mold-like growth of branching hyphae. This transition from yeast to hyphal growth has attracted particular attention, as it has been linked to the virulence of C. albicans as an opportunistic human pathogen. Signal transduction pathways that mediate the induction of the hyphal transcription program upon the imposition of external stimuli have been extensively investigated. However, the hyphal morphogenesis transcription program can also be induced by internal cellular signals, such as inhibition of cell cycle progression, and conversely, the inhibition of hyphal extension can repress hyphal-specific gene expression, suggesting that endogenous cellular signals are able to modulate hyphal gene expression as well. Here we review recent developments in the regulation of the hyphal morphogenesis of C. albicans, with emphasis on endogenous morphogenetic signals.

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“…One striking observation is that, in addition to iron starvation conditions, the CFEM hemophores involved in heme uptake are also among the most strongly induced genes under hyphal induction conditions (Azadmanesh et al, 2017;Roy and Kornitzer, 2019). C. albicans is a dimorphic pathogen, capable of switching from a yeast to a hyphal (mold) morphology under a variety of conditions such as elevated temperature, the presence of serum, the bacterial and fungal cell wall precursor N-acetyl glucosamine, among others (Sudbery et al, 2004;Basso et al, 2019;Kornitzer, 2019). While there is no evidence that the CFEM hemophores are required for hyphal morphogenesis, it is possible that hyphal-inducing conditions signify a heme-rich environment, be it the gut lumen or the mucosal surface, which would promote heme uptake even when iron is relatively abundant.…”

Section: Discussionmentioning

confidence: 99%

Using genetically encoded heme sensors to probe the mechanisms of heme uptake and homeostasis inCandida albicans

Weissman

Pinsky

Donegan

et al. 2020

Preprint

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Candida albicans is a major fungal pathogen that can utilize hemin and hemoglobin as iron sources in the iron-scarce host environment. While C. albicans is a heme prototroph, we show here that it can also efficiently utilize external heme as a cellular heme source. Using genetically encoded ratiometric fluorescent heme sensors, we show that heme extracted from hemoglobin and free hemin enter the cells with different kinetics. Heme supplied as hemoglobin is taken up via the CFEM (Common in Fungal Extracellular Membrane) hemophore cascade, and reaches the cytoplasm over several hours, whereas entry of free hemin via CFEM-dependent and independent pathways is much faster, less than an hour. To prevent an influx of extracellular heme from reaching toxic levels in the cytoplasm, the cells deploy Hmx1, a heme oxygenase. Hmx1 was previously suggested to be involved in utilization of hemoglobin and hemin as iron sources, but we find that it is primarily required to prevent heme toxicity. Taken together, the combination of novel heme sensors with genetic analysis revealed new details of the fungal mechanisms of heme import and homeostasis, necessary to balance the uses of heme as essential cofactor and potential iron source against its toxicity.

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From Genes to Networks: The Regulatory Circuitry Controlling Candida albicans Morphogenesis

Cited by 35 publications

References 276 publications

Mitochondria-Mediated Azole Drug Resistance and Fungal Pathogenicity: Opportunities for Therapeutic Development

Mitochondria-Mediated Azole Drug Resistance and Fungal Pathogenicity: Opportunities for Therapeutic Development

Regulation of Candida albicans Hyphal Morphogenesis by Endogenous Signals

Using genetically encoded heme sensors to probe the mechanisms of heme uptake and homeostasis inCandida albicans

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