LncRNA DINOR is a virulence factor and global regulator of stress responses in Candida auris

Gao, Jiaxin; Chow, Eve W. L.; Wang, Haitao; Xu, Xiaoli; Cai, Chunling; Song, Yabing; Wang, Jianbin; Wang, Yue

doi:10.1038/s41564-021-00915-x

Cited by 51 publications

(48 citation statements)

References 39 publications

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“…In phenotypic analysis, we observed alterations in virulence for the morphogenic mutants, consistent with other published reports 8 , 11 , 12 . We were also interested to observe altered antifungal susceptibility profiles associated with these mutants which may hint at larger roles for the genes of interest.…”

Section: Discussionsupporting

confidence: 92%

“…Furthermore, we developed a new, codon-optimized G418 selectable marker for use in C. auris . Our work, in concert with similar advancements such as successful resistance marker recycling and piggyBac genome-wide transposon mutagenesis in C. auris 8 , 19 , 40 , will promote improved accessibility to mechanistic understanding of the genetic machinery in C. auris .…”

Section: Discussionmentioning

confidence: 90%

“…auris morphogenic mutants exhibit attenuated virulence and altered antifungal susceptibility. Reports of C. auris isolates that exhibit aggregating or elongated cell morphologies have largely suggested these morphogenic variants show reduced virulence in infection models compared to budding yeast wildtype isolates 8,11,12 . We therefore investigated the pathogenic potential of the Δace2, Δtao3, and Δelm1 mutants in a Galleria mellonella model of infection.…”

Section: Wtmentioning

confidence: 99%

“…Depletion of the essential molecular chaperone HSP90 results in elongated cell growth 6 . Genotoxic stress induced by hydroxyurea or deletion of the DNA damage responsive long non-coding RNA DINOR similarly result in pseudohyphal elongated cells 7 , 8 . Other stressors such as growth in high salt concentrations induce cell elongation 9 .…”

Section: Introductionmentioning

confidence: 99%

“…A forward genetics system represents an alternative approach for manipulating the genome. The piggyBac transposon mutagenesis system has proven successful for performing insertional mutagenesis at saturating levels in a Clade II C. auris isolate 8 . This represents a significant advance in the technical ability to genetically manipulate C. auris .…”

Section: Introductionmentioning

confidence: 99%

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Forward and reverse genetic dissection of morphogenesis identifies filament-competent Candida auris strains

Santana

O’Meara

2021

Nat Commun

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Candida auris is an emerging healthcare-associated pathogen of global concern. Recent reports have identified C. auris isolates that grow in cellular aggregates or filaments, often without a clear genetic explanation. To investigate the regulation of C. auris morphogenesis, we applied an Agrobacterium-mediated transformation system to all four C. auris clades. We identified aggregating mutants associated with disruption of chitin regulation, while disruption of ELM1 produced a polarized, filamentous growth morphology. We developed a transiently expressed Cas9 and sgRNA system for C. auris that significantly increased targeted transformation efficiency across the four C. auris clades. Using this system, we confirmed the roles of C. auris morphogenesis regulators. Morphogenic mutants showed dysregulated chitinase expression, attenuated virulence, and altered antifungal susceptibility. Our findings provide insights into the genetic regulation of aggregating and filamentous morphogenesis in C. auris. Furthermore, the genetic tools described here will allow for efficient manipulation of the C. auris genome.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 90%

Section: Wtmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Forward and reverse genetic dissection of morphogenesis identifies filament-competent Candida auris strains

Santana

O’Meara

2021

Nat Commun

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RNA as a Mediator of Host-Fungal Pathogenesis

Bruch,

Blango

2024

The Mycota

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In silico genome wide identification of long non-coding RNAs differentially expressed during Candida auris host pathogenesis

Mathur,

Singh,

Puria

et al. 2024

Arch Microbiol

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Candida auris is an invasive fungal pathogen of high concern due to acquired drug tolerance against antifungals used in clinics. The prolonged persistence on biotic and abiotic surfaces can result in onset of hospital outbreaks causing serious health threat. An in depth understanding of pathology of C. auris is highly desirable for development of e cient therapeutics. Non coding RNAs play crucial role in fungal pathology. However, the information about ncRNAs is scanty to be utilized. Herein our aim is to identify long noncoding RNAs with potent role in pathobiology of C. auris. Thereby, we analyzed the transcriptomics data of C. auris infection in blood for identi cation of potential lncRNAs with regulatory role in determining invasion, survival or drug tolerance under infection conditions. Interestingly, we found 275 lncRNAs, out of which 253 matched with lncRNAs reported in Candidamine, corroborating for our accurate data analysis pipeline. Nevertheless, we obtained 23 novel lncRNAs not reported earlier. Three lncRNAs were found to be under expressed throughout the course of infection, in the transcriptomics data. 16 of potent lncRNAs were found to be coexpressed with coding genes, emphasizing for their functional role. Noteworthy, these ncRNAs are expressed from intergenic regions of the genes associated with transporters, metabolism, cell wall biogenesis. This study recommends for possible association between lncRNA expression and C. auris pathogenesis.

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LncRNA DINOR is a virulence factor and global regulator of stress responses in Candida auris

Cited by 51 publications

References 39 publications

Forward and reverse genetic dissection of morphogenesis identifies filament-competent Candida auris strains

Forward and reverse genetic dissection of morphogenesis identifies filament-competent Candida auris strains

RNA as a Mediator of Host-Fungal Pathogenesis

In silico genome wide identification of long non-coding RNAs differentially expressed during Candida auris host pathogenesis

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