Ssn6 has dual roles in <i>Candida albicans</i> filament development through the interaction with Rpd31

Lee, Jieun; Oh, Jang-Hyun; Ku, MyungHee; Kim, Jueun; Lee, Jung Shin; Kang, Sa-Ouk

doi:10.1016/j.febslet.2015.01.011

Cited by 22 publications

(22 citation statements)

References 55 publications

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“…Several previous studies suggest that chromatin alterations contribute to yeast-to-hyphae transitions 16 , 17 , 19 , 21 , 37 , 38 . Moreover, recent work also uncovered a role of the HIR histone chaperone member Hir1 in white-opaque switching 29 and azole tolerance 30 in C .…”

Section: Resultsmentioning

confidence: 98%

The Candida albicans HIR histone chaperone regulates the yeast-to-hyphae transition by controlling the sensitivity to morphogenesis signals

Jenull

Tscherner

Gulati

et al. 2017

Sci Rep

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Morphological plasticity such as the yeast-to-hyphae transition is a key virulence factor of the human fungal pathogen Candida albicans. Hyphal formation is controlled by a multilayer regulatory network composed of environmental sensing, signaling, transcriptional modulators as well as chromatin modifications. Here, we demonstrate a novel role for the replication-independent HIR histone chaperone complex in fungal morphogenesis. HIR operates as a crucial modulator of hyphal development, since genetic ablation of the HIR complex subunit Hir1 decreases sensitivity to morphogenetic stimuli. Strikingly, HIR1-deficient cells display altered transcriptional amplitudes upon hyphal initiation, suggesting that Hir1 affects transcription by establishing transcriptional thresholds required for driving morphogenetic cell-fate decisions. Furthermore, ectopic expression of the transcription factor Ume6, which facilitates hyphal maintenance, rescues filamentation defects of hir1Δ/Δ cells, suggesting that Hir1 impacts the early phase of hyphal initiation. Hence, chromatin chaperone-mediated fine-tuning of transcription is crucial for driving morphogenetic conversions in the fungal pathogen C. albicans.

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Section: Resultsmentioning

confidence: 98%

The Candida albicans HIR histone chaperone regulates the yeast-to-hyphae transition by controlling the sensitivity to morphogenesis signals

Jenull

Tscherner

Gulati

et al. 2017

Sci Rep

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“…The NAD + ‐dependent KDAC inhibitor nicotinamide has been shown to reduce fungal kidney burden in a mouse model of disseminated candidiasis (Wurtele et al ., ). Also, an rpd31Δ/rpd31Δ mutant has attenuated virulence in a mouse model of systemic infection (Lee et al ., ). Although we observed that some Candida species and some C. albicans clinical isolates maintained azole resistance in the presence of Hsp90 or KDAC inhibitors, targeting Hsp90 and KDACs may still possess great therapeutic potential against these organisms.…”

Section: Discussionmentioning

confidence: 97%

Extensive functional redundancy in the regulation of Candida albicans drug resistance and morphogenesis by lysine deacetylases Hos2, Hda1, Rpd3 and Rpd31

Robbins

O’Meara

et al. 2016

Molecular Microbiology

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Summary Current treatment efforts for fungal infections are hampered by the limited availability of antifungal drugs and by the emergence of drug resistance. A powerful strategy to enhance the efficacy of antifungal drugs is to inhibit the molecular chaperone Hsp90. Hsp90 governs drug resistance, morphogenesis, and virulence in a leading fungal pathogen of humans, Candida albicans. Our previous work with Saccharomyces cerevisiae established acetylation as a novel mechanism of posttranslational control of Hsp90 function in fungi. We implicated lysine deacetylases (KDACs) as key regulators of resistance to the most widely deployed class of antifungals, the azoles, in both S. cerevisiae and C. albicans. Here, we demonstrate high levels of functional redundancy among the KDACs that are important for regulating Hsp90 function. We identify Hos2, Hda1, Rpd3, and Rpd31 as the KDACs mediating azole resistance and morphogenesis in C. albicans. Furthermore, we identify lysine 30 and 271 as critical acetylation sites on C. albicans Hsp90, and substitutions at these residues compromised Hsp90 function. Finally, we show that pharmacological inhibition of KDACs phenocopies pharmacological inhibition of Hsp90 and abrogates Hsp90-dependent azole resistance in numerous Candida species. This work illuminates new facets to the impact of KDACs on fungal drug resistance and morphogenesis, provides important insights into the divergence of the C. albicans Hsp90 regulatory network, and reveals new targets for development of antifungal drugs.

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“…The KDAC, Ca_RPD31, has dual functionality in regulating hyphal morphogenesis in C. albicans . Phenotypic analysis of Ca_rpd31Δ/Δ shows that it does not form hyphae under conditions that stimulate Y-H transition [ 111 ]. However, under non-hyphal inducing conditions, and when combined with a mutation in the transcription factor Ca_SSN6 (Ca_ssn6Δ/Δ), lack of Ca_RPD31 activity promote s hyphal development.…”

Section: Candida Spp Phenotypic Plasticity Andmentioning

confidence: 99%

Chromatin Structure and Drug Resistance in Candida spp.

O'Kane

Weild

Hyland

2020

JoF

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Anti-microbial resistance (AMR) is currently one of the most serious threats to global human health and, appropriately, research to tackle AMR garnishes significant investment and extensive attention from the scientific community. However, most of this effort focuses on antibiotics, and research into anti-fungal resistance (AFR) is vastly under-represented in comparison. Given the growing number of vulnerable, immunocompromised individuals, as well as the positive impact global warming has on fungal growth, there is an immediate urgency to tackle fungal disease, and the disturbing rise in AFR. Chromatin structure and gene expression regulation play pivotal roles in the adaptation of fungal species to anti-fungal stress, suggesting a potential therapeutic avenue to tackle AFR. In this review we discuss both the genetic and epigenetic mechanisms by which chromatin structure can dictate AFR mechanisms and will present evidence of how pathogenic yeast, specifically from the Candida genus, modify chromatin structure to promote survival in the presence of anti-fungal drugs. We also discuss the mechanisms by which anti-chromatin therapy, specifically lysine deacetylase inhibitors, influence the acquisition and phenotypic expression of AFR in Candida spp. and their potential as effective adjuvants to mitigate against AFR.

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Ssn6 has dual roles in Candida albicans filament development through the interaction with Rpd31

Cited by 22 publications

References 55 publications

The Candida albicans HIR histone chaperone regulates the yeast-to-hyphae transition by controlling the sensitivity to morphogenesis signals

The Candida albicans HIR histone chaperone regulates the yeast-to-hyphae transition by controlling the sensitivity to morphogenesis signals

Extensive functional redundancy in the regulation of Candida albicans drug resistance and morphogenesis by lysine deacetylases Hos2, Hda1, Rpd3 and Rpd31

Chromatin Structure and Drug Resistance in Candida spp.

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