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Cited by 44Antifungal resistance and susceptibilityFungal and yeast genetics researchFungal Infections and Studies

Candida auris undergoes adhesin-dependent and -independent cellular aggregation

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Pelletier, Chloe, Shaw, Sophie, Alsayegh, Sakinah, Brown, Alistair J. P., Lorenz, Alexander·2024·PLOS Pathogens
DOI 10.1371/journal.ppat.1012076PMC PMC10957086

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Abstract

Candida auris is a fungal pathogen of humans responsible for nosocomial infections with high mortality rates. High levels of resistance to antifungal drugs and environmental persistence mean these infections are difficult to treat and eradicate from a healthcare setting. Understanding the life cycle and the genetics of this fungus underpinning clinically relevant traits, such as antifungal resistance and virulence, is of the utmost importance to develop novel treatments and therapies. Epidemiological and genomic studies have identified five geographical clades (I-V), which display phenotypic and genomic differences. Aggregation of cells, a phenotype primarily of clade III strains, has been linked to reduced virulence in some infection models. The aggregation phenotype has thus been associated with conferring an advantage for (skin) colonisation rather than for systemic infection. However, strains with different clade affiliations were compared to infer the effects of different morphologies on virulence. This makes it difficult to distinguish morphology-dependent causes from clade-specific or even strain-specific genetic factors. Here, we identify two different types of aggregation: one induced by antifungal treatment which is a result of a cell separation defect; and a second which is controlled by growth conditions and only occurs in strains with the ability to aggregate. The latter aggregation type depends on an ALS-family adhesin which is differentially expressed during aggregation in an aggregative C . auris strain. Finally, we demonstrate that macrophages cannot clear aggregates, suggesting that aggregation might after all provide a benefit during systemic infection and could facilitate long-term persistence in the host.

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Crossref · 10.1371/journal.ppat.1012076

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  • A recent in vitro study on co-culturing of the aggregative phenotype of C. auris with macrophage demonstrated that the macrophage does not recognize and clear the aggregates due to the morphology.

    “A recent in vitro study on co-culturing of the aggregative phenotype of C. auris with macrophage demonstrated that the macrophage does not recognize and clear the aggregates due to the morphology (18).”

    From Cell aggregation mediated by <i>ACE2</i> deletion in <i>Candida auris</i> modulates fungal colonization and host immune responses in the skin (2024) · cites this paper as [18]

    The Results section (‘Aggregates are not cleared by macrophages’; page not provided) reports that macrophages struggled to engulf aggregates and that their ability to clear them was dampened. It explicitly says there was no issue sensing C. auris under aggregating conditions, so the claim that macrophages did not recognize the aggregates is not supported. (LLM, conf=0.90)

    Experimental — accuracy not yet measured

  • 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 [72]

    The Results section (“Als4112 is necessary for aggregation”; page not provided) reports that loss of ALS4112 prevented media-induced aggregation and that complementation restored it. The Discussion describes a link between ALS4112 copy-number variation and biofilm-forming capability as apparent, citing earlier work; it does not establish the unqualified claim that Als4112 enhances biofilm formation. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • In clade III, the adhesin Als4112 plays a key role in aggregation via copy number variation.

    “In clade III, the adhesin Als4112 (SBP28_005090/B9J08_004112) was shown to play a key role in aggregation via copy number variation (24, 49).”

    From Ume6-dependent pathways of morphogenesis and biofilm formation in <i>Candida auris</i> (2024) · cites this paper as [49]

    The Results section (‘Als4112 is necessary for aggregation’; page not provided) shows that disrupting ALS4112 prevented media-induced aggregation in a clade III strain and that adding the gene back restored it. The Discussion proposes copy-number variation as an explanation, drawing on an earlier study, but does not establish it as the mechanism in the strain tested; ALS4112 was not required for echinocandin-induced clustering. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • C. auris can undergo adhesin-dependent and -independent aggregation.

    “Broadly, C. auris can undergo adhesin-dependent and -independent aggregation (18).”

    From Cell aggregation mediated by <i>ACE2</i> deletion in <i>Candida auris</i> modulates fungal colonization and host immune responses in the skin (2024) · cites this paper as [18]

  • Aggregation is mainly observed among clade III isolates but has also been reported in other clades.

    “Aggregation has been mainly observed among clade III isolates but has also been reported in other clades and can be induced under some in vitro or in vivo conditions (18, 49–51).”

    From Ume6-dependent pathways of morphogenesis and biofilm formation in <i>Candida auris</i> (2024) · cites this paper as [49]

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Research works printed but not linked: 46

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Cited by

Sorted by citations

Authors
Pelletier, C., Shaw, S., Alsayegh, S., Brown, A. J. P., & Lorenz, A.
Affiliations
  • University of Aberdeen (GB)
  • University of Exeter (GB)
Corresponding author
Lorenz, Alexander
ORCID
Venue
PLOS Pathogens
Publisher
Public Library of Science (PLoS)
Published
2024-03-11
Volume
20
Issue
3
Pages
e1012076
ISSN
  • 1553-7366 (ISSN-L)
  • 1553-7374
DOI
10.1371/journal.ppat.1012076
PMC
PMC10957086
OpenAlex
W4392639057
Cited by
44
References
8
Citations by year
2026: 12 · 2025: 19 · 2024: 11 · 2023: 2
FWCI
14.53
Type
journal article
Language
en
Update notices
new_version (2024-03-21)
Open access
Licence
Locations
  • PLoS Pathogens (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Aberdeen University Research Archive (Aberdeen University) (acceptedVersion, cc-by-nc-nd)
  • Aberdeen University Research Archive (Aberdeen University) (submittedVersion, cc-by-nc-nd)
  • Aberdeen University Research Archive (Aberdeen University) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
Medical Research Council Centre for Medical Mycology (MR/P501955/1, MR/N006364/2)
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, cell aggregation, adhesins, fungal clades, virulence, antifungal resistance, macrophage clearance, fungal morphology, skin colonization, systemic infection, host persistence
MeSH terms
Candida auris, Antifungal Agents, Candida, Humans, Microbial Sensitivity Tests, Virulence, Adhesins, Bacterial, Drug Resistance, Fungal

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