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Cited by 84Antifungal resistance and susceptibilityFungal and yeast genetics researchYeasts and Rust Fungi Studies

Clinical isolates of Candida auris with enhanced adherence and biofilm formation due to genomic amplification of ALS4

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Bing, Jian, Guan, Zhangyue, Zheng, Tianhong, Zhang, Zhijie, Fan, Shuru, Ennis, Craig L., Nobile, Clarissa J., Huang, Guanghua·2023·PLOS Pathogens
DOI 10.1371/journal.ppat.1011239PMC PMC10035925
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Abstract

Candida auris is an emerging multidrug-resistant fungal pathogen and a new global threat to human health. A unique morphological feature of this fungus is its multicellular aggregating phenotype, which has been thought to be associated with defects in cell division. In this study, we report a new aggregating form of two clinical C . auris isolates with increased biofilm forming capacity due to enhanced adherence of adjacent cells and surfaces. Unlike the previously reported aggregating morphology, this new aggregating multicellular form of C . auris can become unicellular after treatment with proteinase K or trypsin. Genomic analysis demonstrated that amplification of the subtelomeric adhesin gene ALS4 is the reason behind the strain’s enhanced adherence and biofilm forming capacities. Many clinical isolates of C . auris have variable copy numbers of ALS4 , suggesting that this subtelomeric region exhibits instability. Global transcriptional profiling and quantitative real-time PCR assays indicated that genomic amplification of ALS4 results in a dramatic increase in overall levels of transcription. Compared to the previously characterized nonaggregative/yeast-form and aggregative-form strains of C . auris , this new Als4-mediated aggregative-form strain of C . auris displays several unique characteristics in terms of its biofilm formation, surface colonization, and virulence.

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Crossref · 10.1371/journal.ppat.1011239

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  • Copy number variation of ALS4 accounts for variation in biofilm formation, surface colonization, and virulence among C. auris isolates, and Als4 amplification is linked to improved skin colonization during natural evolution.

    “Bing and colleagues showed that copy number variation of ALS4 accounts for variation in biofilm formation, surface colonization, and virulence among isolates, linking Als4 amplification to improved skin colonization during natural evolution31.”

    From Adhesin Als4112 promotes Candida auris skin colonization through interactions with keratinocytes and extracellular matrix proteins (2025) · cites this paper as [31]

    The Results sections on ALS4 copy-number variation and skin colonization link amplified ALS4 to enhanced biofilm formation and show that strain SJ02 colonized newborn mouse skin more robustly than the comparison strains. The virulence Results report decreased, not increased, virulence for SJ02 in a Galleria infection model. The paper documents copy-number changes in clinical isolates, but does not show that ALS4 amplification improved skin colonization during natural evolution. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Clinical isolates of C. auris exhibiting aggregative phenotypes often harbor amplification of the sub-telomeric ALS4112 locus, conferring robust biofilm formation and colonization on murine skin.

    “Clinical isolates of C. auris exhibiting aggregative phenotypes often harbor amplification of the sub-telomeric ALS4112 locus, conferring robust biofilm formation and colonization on murine skin [73].”

    From Host–Candida auris interactions in the skin (2026) · cites this paper as [73]

    The Results sections on ALS4 genomic analysis and newborn-mouse skin colonization report that amplified ALS4 contributes to a new aggregative phenotype and that strain SJ02 formed robust biofilms and colonized mouse skin. The claim overgeneralizes this to aggregative isolates ‘often’ harboring amplification: the paper distinguishes another aggregative phenotype, and its surveyed isolates rarely had more than two ALS4 copies. The locus is named ALS4 (also B9J08_004112), not ALS4112; murine skin colonization was demonstrated for SJ02, not for aggregative isolates generally (pages unavailable in our copy). (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Biofilm formation enhances Candida auris adhesive capacity and colonization efficiency.

    “with biofilm formation enhancing its adhesive capacity and colonization efficiency9–11”

    From The Wor2 phenotypic switching regulator controls biofilm formation in Candida auris (2026) · cites this paper as [9]

    The Results section on skin colonization (page unavailable) reports that the strain with robust biofilms also showed the strongest colonization of newborn mouse skin. The Discussion (page unavailable) attributes enhanced adherence and biofilm formation to ALS4 amplification; it does not show that biofilm formation itself increases adhesive capacity or causes more efficient colonization. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • A previous report showed a correlation between genomic amplification of ALS4 and enhanced skin colonization in C. auris clinical isolates.

    “This is consistent with a previous report showing a correlation between genomic amplification of ALS4 and enhanced skin colonization in C. auris clinical isolates31.”

    From Adhesin Als4112 promotes Candida auris skin colonization through interactions with keratinocytes and extracellular matrix proteins (2025) · cites this paper as [31]

  • Als4112 enhances C. auris cell aggregation and biofilm formation.

    “Als4112, a member of the agglutinin-like sequence (Als) adhesin family, further enhances C. auris cell aggregation and biofilm formation [72,73].”

    From Host–Candida auris interactions in the skin (2026) · cites this paper as [73]

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Sorted by citations

Authors
Bing, J., Guan, Z., Zheng, T., Zhang, Z., Fan, S., Ennis, C. L., Nobile, C. J., & Huang, G.
Affiliations
  • Fudan University (CN)
  • Sheng Jing Hospital (CN)
  • University of California, Merced (US)
Corresponding author
Huang, Guanghua
ORCID
Venue
PLOS Pathogens
Publisher
Public Library of Science (PLoS)
Published
2023-03-13
Volume
19
Issue
3
Pages
e1011239
ISSN
  • 1553-7366 (ISSN-L)
  • 1553-7374
DOI
10.1371/journal.ppat.1011239
PMC
PMC10035925
OpenAlex
W4324020291
Cited by
84
References
7
Citations by year
2026: 26 · 2025: 27 · 2024: 22 · 2023: 9
FWCI
17.39
Type
journal article
Language
en
Update notices
new_version (2023-03-23)
Open access
Licence
Locations
  • PLoS Pathogens (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Natural Science Foundation of China (31930005, 32000018 and 32170193)
  • Key Technologies Research and Development Program (2021YFC2300400)
  • National Institute of General Medical Sciences (R35GM124594)
  • The Kamangar family in the form of an endowed chair
Topics
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Yeasts and Rust Fungi Studies
Keywords
Candida auris, biofilm formation, cell adhesion, copy number variation, surface colonization, virulence, multidrug resistance, clinical isolates
MeSH terms
Candida auris, Antifungal Agents, Candida, Humans, Microbial Sensitivity Tests, Biofilms, Genomics

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