Clade-specific chromosomal rearrangements and loss of subtelomeric adhesins in Candida auris
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Abstract
Candida auris is an emerging fungal pathogen of rising concern due to global spread, the ability to cause healthcare-associated outbreaks, and antifungal resistance. Genomic analyses revealed that early contemporaneously detected cases of C. auris were geographically stratified into four major clades. While Clades I, III, and IV are responsible for ongoing outbreaks of invasive and multidrug-resistant infections, Clade II, also termed the East Asian clade, consists primarily of cases of ear infection, is often susceptible to all antifungal drugs, and has not been associated with outbreaks. Here, we generate chromosome-level assemblies of twelve isolates representing the phylogenetic breadth of these four clades and the only isolate described to date from Clade V. This Clade V genome is highly syntenic with those of Clades I, III, and IV, although the sequence is highly divergent from the other clades. Clade II genomes appear highly rearranged, with translocations occurring near GC-poor regions, and large subtelomeric deletions in most chromosomes, resulting in a substantially different karyotype. Rearrangements and deletion lengths vary across Clade II isolates, including two from a single patient, supporting ongoing genome instability. Deleted subtelomeric regions are enriched in Hyr/Iff-like cell-surface proteins, novel candidate cell wall proteins, and an ALS-like adhesin. Cell wall proteins from these families and other drug-related genes show clade-specific signatures of selection in Clades I, III, and IV. Subtelomeric dynamics and the conservation of cell surface proteins in the clades responsible for global outbreaks causing invasive infections suggest an explanation for the different phenotypes observed between clades.
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The C. auris genome codes for several species-specific cell surface glycoproteins that may facilitate C. auris adhesion to different substrates.
“the C. auris genome codes for several species-specific cell surface glycoproteins that may facilitate C. auris adhesion to different substrates (20, 22).”
From The <i>Candida auris</i> Hog1 MAP kinase is essential for the colonization of murine skin and intradermal persistence (2024) · cites this paper as [20]
The Results section (page unavailable) identifies several predicted GPI-anchored cell-wall proteins as candidate adhesins, supporting a possible role in adhesion. It does not establish adhesion to different substrates, and the relevant proteins are not strictly species-specific: the paper also finds them in closely related species. (LLM, conf=0.85)
Experimental — accuracy not yet measuredThere are clade-specific differences in adhesin expression between C. auris isolates.
“there are clade-specific differences in adhesin expression between the C. auris isolates (20).”
From The <i>Candida auris</i> Hog1 MAP kinase is essential for the colonization of murine skin and intradermal persistence (2024) · cites this paper as [20]
The Results section reports that Clade II lacks fourteen candidate adhesin genes present in other C. auris clades. It does not establish clade-specific differences in adhesin expression between isolates; the expression findings it cites concern biofilm growth or other conditions, not comparisons between clades. (LLM, conf=0.85)
Experimental — accuracy not yet measuredOnly 3 ALS genes have been identified in C. auris, unlike C. albicans which contains at least 11 Als adhesins.
“unlike C. albicans, which contains at least 11 Als adhesins, thus far only 3 ALS genes have been identified in C. auris (20, 22).”
From The <i>Candida auris</i> Hog1 MAP kinase is essential for the colonization of murine skin and intradermal persistence (2024) · cites this paper as [20]
The Discussion (page unavailable) names three distinct C. auris ALS-related genes: an ALS4 homolog, a potential ALS adhesin, and ALS3. It does not say that only three ALS genes have been identified in C. auris, or that C. albicans has at least 11 Als adhesins. (LLM, conf=0.84)
Experimental — accuracy not yet measuredC. auris displays at least three Als-like, eight Hyr/Iff-like, and one species-specific adhesin (Scf1).
“C. auris displays at least three Als-like, eight Hyr/Iff-like, and one species-specific adhesin (Scf1) (27, 53–55) (Table S3).”
From Ume6-dependent pathways of morphogenesis and biofilm formation in <i>Candida auris</i> (2024) · cites this paper as [53]
The Results section on depleted Hyr/Iff proteins reports eight Hyr/Iff proteins in C. auris. The Discussion identifies several Als-like genes, but the copy does not establish a count of at least three distinct ones. No passage found identifies Scf1 as a species-specific adhesin; the species-specific candidate family discussed in Results is also found in closely related species. Page numbers were not available in the indexed copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe genome of C. auris contains adhesins belonging to the ALS and IFF/HYR families.
“The genome of C. auris is reported to contain adhesins belonging to ALS and the IFF/HYR family (20, 22).”
From The <i>Candida auris</i> Hog1 MAP kinase is essential for the colonization of murine skin and intradermal persistence (2024) · cites this paper as [20]
Most fluconazole-resistant C. auris isolates studied to date carry mutations in both TAC1B and ERG11.
“Indeed, most fluconazole-resistant C. auris isolates studied to date carry mutations in both TAC1B and ERG11 (17).”
From Delineation of the Direct Contribution of Candida auris <i>ERG11</i> Mutations to Clinical Triazole Resistance (2021) · cites this paper as [17]
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Self-citationRybak, J. M., Sharma, C., Doorley, L. A., Barker, K. S., Palmer, G. E., & Rogers, P. D. (2021) · Microbiology Spectrum · doi:10.1128/spectrum.01585-21 · Cited by 69 · see citing works
Mechanisms of pathogenicity for the emerging fungus Candida auris
Horton, M. V., Holt, A. M., & Nett, J. E. (2023) · PLOS Pathogens · doi:10.1371/journal.ppat.1011843 · Cited by 67 · see citing works
Codda, G., Willison, E., Magnasco, L., Morici, P., Giacobbe, D. R., Mencacci, A., Marini, D., Mikulska, M., Bassetti, M., Marchese, A., et al. (2023) · Eurosurveillance · doi:10.2807/1560-7917.es.2023.28.14.2300161 · Cited by 44 · see citing works
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“For instance, clade II isolates show a propensity for ear infections (60); they lost genes encoding putative adhesins (61) and harbor”
BackgroundDatta, A., Das, D., Nett, J. E., Vyas, J. M., Lionakis, M. S., & Thangamani, S. (2023) · Microbiology Spectrum · doi:10.1128/spectrum.02215-23 · Cited by 30 · see citing works
“auris from skin surface to the dermis, which is an important future area to investigate (21).”
BackgroundThe skin mycobiome and intermicrobial interactions in the cutaneous niche
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Shivarathri, R., Chauhan, M., Datta, A., Das, D., Karuli, A., Aptekmann, A., Jenull, S., Kuchler, K., Thangamani, S., Chowdhary, A., et al. (2024) · mBio · doi:10.1128/mbio.02748-24 · Cited by 22 · see citing works
“Furthermore, the C. auris genome codes for several species-specific cell surface glycoproteins that may facilitate C. auris adhesion to different substrates (20, 22).”
InfluentialUme6-dependent pathways of morphogenesis and biofilm formation in <i>Candida auris</i>
Louvet, M., Li, J., Brandalise, D., Bachmann, D., Sala de Oyanguren, F., Labes, D., Jacquier, N., Genoud, C., Mucciolo, A., Coste, A. T., et al. (2024) · Microbiology Spectrum · doi:10.1128/spectrum.01531-24 · Cited by 20 · see citing works
- Authors
- Muñoz, J. F., Welsh, R. M., Shea, T., Batra, D., Gade, L., Howard, D., Rowe, L. A., Meis, J. F., Litvintseva, A. P., & Cuomo, C. A.
- Affiliations
- Broad Institute (US)
- Mycotic Diseases Branch, U.S. Department of Health and Human Services , Atlanta, GA, USA
- Centers for Disease Control and Prevention (US)
- Radboud University Medical Center (NL)
- Corresponding author
- Cuomo, Christina A
- ORCID
- Venue
- Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2021-03-26
- Volume
- 218
- Issue
- 1
- ISSN
- 0016-6731 (ISSN-L)
- 1943-2631
- PMC
- PMC8128392
- OpenAlex
- W3130607038
- Cited by
- 125
- References
- 66
- Citations by year
- 2026: 22 · 2025: 23 · 2024: 28 · 2023: 19 · 2022: 12 · 2021: 17 · 2020: 4
- FWCI
- 6.02
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Genetics (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institute of Allergy and Infectious Diseases
- National Institutes of Health
- Department of Health and Human Services (U19AI110818)
- Broad Institute
- Fungal Kingdom Program
- 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, subtelomeric deletion, chromosome-level genome assembly, karyotype, translocation, genomic instability, cell surface adhesins, cell wall proteins, positive selection, antifungal resistance, invasive candidiasis
- MeSH terms
- Candida auris, Candida, Chromosome Aberrations, Chromosomes, Phylogeny, Gene Rearrangement, Telomere, Genome, Fungal, Genomics, Karyotype
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