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Cited by 176Antifungal resistance and susceptibilityFungal and yeast genetics researchFungal Infections and Studies

Filamentation in Candida auris , an emerging fungal pathogen of humans: passage through the mammalian body induces a heritable phenotypic switch

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Yue, Huizhen, Bing, Jian, Zheng, Qiushi, Zhang, Yulong, Hu, Tianren, Du, Han, Wang, Hui, Huang, Guanghua·2018·Emerging Microbes & Infections
DOI 10.1038/s41426-018-0187-xPMC PMC6258701
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Abstract

Morphological plasticity has historically been an indicator of increased virulence among fungal pathogens, allowing rapid adaptation to changing environments. Candida auris has been identified as an emerging multidrug-resistant human pathogen of global importance. Since the discovery of this species, it has been thought that C. auris is incapable of filamentous growth. Here, we report the discovery of filamentation and three distinct cell types in C. auris: typical yeast, filamentation-competent (FC) yeast, and filamentous cells. These cell types form a novel phenotypic switching system that contains a heritable (typical yeast-filament) and a nonheritable (FC-filament) switch. Intriguingly, the heritable switch between the typical yeast and the FC/filamentous phenotype is triggered by passage through a mammalian body, whereas the switch between the FC and filamentous phenotype is nonheritable and temperature-dependent. Low temperatures favor the filamentous phenotype, whereas high temperatures promote the FC yeast phenotype. Systemic in vivo and in vitro investigations were used to characterize phenotype-specific variations in global gene expression, secreted aspartyl proteinase (SAP) activity, and changes in virulence, indicating potential for niche-specific adaptations. Taken together, our study not only sheds light on the pathogenesis and biology of C. auris but also provides a novel example of morphological and epigenetic switching in fungi.

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  • Some genes expressed in C. albicans hyphal phase have no orthologs in C. auris or no significant change of expression in different conditions inducing C. auris filamentation.

    “Moreover, some genes expressed in C. albicans hyphal phase have no orthologs in C. auris (e.g., ECE1, HWP1) or no significant change of expression in different conditions inducing C. auris filamentation (e.g., FLO8, EFG1, BRG1, BCR1, EFH1), suggesting distinct pathways between these genotypically distant Candida spp. (20, 37, 47).”

    From Ume6-dependent pathways of morphogenesis and biofilm formation in <i>Candida auris</i> (2024) · cites this paper as [20]

    The Results section (page not available) says FLO8 was upregulated and EFG1 was downregulated in filamentous C. auris cells, contrary to the claim that they showed no significant expression change. The retrieved passages do not establish whether ECE1 or HWP1 lack C. auris orthologs. (LLM, conf=0.88)

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  • Genes involved in filamentous growth (HGC1, DDR48, PHR1) are upregulated in UME6HA and in the filamentous phenotype of C. auris following passage through the mammalian body.

    “For instance, genes involved in filamentous growth (HGC1, DDR48, PHR1) were upregulated in UME6HA and in the filamentous phenotype of C. auris following passage through the mammalian body (20).”

    From Ume6-dependent pathways of morphogenesis and biofilm formation in <i>Candida auris</i> (2024) · cites this paper as [20]

    The Results section on global gene expression reports that HGC1 was upregulated in filamentous C. auris cells, and the Results section on mammalian passage reports that passage through mice triggered a filamentous phenotype (page numbers unavailable). Our copy does not report upregulation of DDR48 or PHR1, or mention UME6HA; searches for those terms found no supporting passage. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Clinical isolates of C. auris can exhibit different morphotypes such as filamentous, pseudohyphal, and yeast forms.

    “Clinical isolates of C. auris can exhibit different morphotypes such as filamentous, pseudohyphal, and yeast forms (8–14).”

    From Yeast and filamentous <i>Candida auris</i> stimulate distinct immune responses in the skin (2024) · cites this paper as [13]

  • GSEA shows significant overlap between UME6HA upregulated genes and genes upregulated by the in vivo yeast to filament transition.

    “As shown in Fig. S3, the resulting network of data sets showed significant overlap with RNAseq profiles of genes upregulated by the in vivo yeast to filament transition [node “FILAMENT VS YEAST_UP” (20)].”

    From Ume6-dependent pathways of morphogenesis and biofilm formation in <i>Candida auris</i> (2024) · cites this paper as [20]

  • Filamentation is an important virulence trait of C. albicans, but its pathogenic role in C. auris is less obvious.

    “While filamentation is an important virulence trait of C. albicans, its pathogenic role in C. auris is less obvious (20, 43, 46).”

    From Ume6-dependent pathways of morphogenesis and biofilm formation in <i>Candida auris</i> (2024) · cites this paper as [20]

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Cited by

Sorted by citations

Authors
Yue, H., Bing, J., Zheng, Q., Zhang, Y., Hu, T., Du, H., Wang, H., & Huang, G.
Affiliations
  • Chinese Academy of Sciences (CN)
  • Fudan University (CN)
  • Peking University People's Hospital (CN)
Corresponding author
Huang, Guanghua
ORCID
Venue
Emerging Microbes & Infections
Publisher
Informa UK Limited
Published
2018-11-28
Volume
7
Issue
1
Pages
1-13
ISSN
2222-1751 (ISSN-L)
DOI
10.1038/s41426-018-0187-x
PMC
PMC6258701
OpenAlex
W2900853140
Cited by
176
References
1
Citations by year
2026: 22 · 2025: 24 · 2024: 28 · 2023: 25 · 2022: 19 · 2021: 18 · 2020: 26 · 2019: 14
FWCI
10.97
Type
journal article
Language
en
Open access
Licence
Locations
  • Emerging Microbes & Infections (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Natural Science Foundation of China (National Science Foundation of China) (31625002 and 31370175)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
  • Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
Keywords
Candida auris, filamentation, phenotypic switching, morphological plasticity, temperature-dependent switching, virulence, secreted aspartyl proteinases, gene expression, epigenetic switching, fungal pathogenesis, multidrug resistance
MeSH terms
Animals, Candida, Candidiasis, Cell Compartmentation, Female, Humans, Mice, Inbred BALB C, Phenotype, Temperature, Virulence, Gene Expression Regulation, Fungal, Gene Expression Profiling, Hyphae, Epigenesis, Genetic, Mice, Host-Pathogen Interactions, Aspartic Acid Proteases

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