Emerging fungal pathogen Candida auris evades neutrophil attack
Open accessAbstract
Candida auris has recently emerged as the first fungal pathogen to cause a global public health threat. The reason this species is causing hospital-associated outbreaks of invasive candidiasis with high mortality is unknown. In this study, we examine the interaction of C. auris with neutrophils, leukocytes critical for control of invasive fungal infections. We show that human neutrophils do not effectively kill C. auris . Compared to Candida albicans , neutrophils poorly recruited to C. auris and failed to form neutrophil extracellular traps (NETs), which are structures of DNA, histones, and proteins with antimicrobial activity. In mixed cultures, neutrophils preferentially engaged and killed C. albicans over C. auris . Imaging of neutrophils in a zebrafish larval model of invasive candidiasis revealed the recruitment of approximately 50% fewer neutrophils in response to C. auris compared to C. albicans . Upon encounter with C. albicans in the zebrafish hindbrain, neutrophils produced clouds of histones, suggesting the formation of NETs. These structures were not observed in C. auris infection. Evasion of neutrophil attack and innate immunity offers an explanation for the virulence of this pathogen. IMPORTANCE The emerging fungal pathogen Candida auris has produced numerous outbreaks of invasive disease in hospitals worldwide. Why this species causes deadly disease is unknown. Our findings reveal a failure of neutrophils to kill C. auris compared to the most commonly encountered Candida species, C. albicans . While neutrophils produce neutrophil extracellular traps (NETs) upon encounter with C. albicans , these antimicrobial structures are not formed in response to C. auris . Using human neutrophils and a zebrafish model of invasive candidiasis, we show that C. auris poorly recruits neutrophils and evades immune attack. Identification of this impaired innate immune response to C. auris sheds light on the dismal outcomes for patients with invasive disease.
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Cell wall mannan masks immunostimulatory cell wall components preventing host cell recognition.
“Similarly, cell wall mannan masks immunostimulatory cell wall components preventing host cell recognition (15, 21).”
From Dual function of <i>Candida auris</i> mannosyltransferase, MNT5, in biofilm community protection from antifungal therapy and the host (2025) · cites this paper as [21]
The OBSERVATION section reports that human neutrophils rarely engaged C. auris and proposes that it goes unrecognized by them. It does not establish that cell wall mannan masks immunostimulatory components or causes this evasion; the authors say the molecular mechanisms remain to be unraveled. No page numbers are provided in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredCell wall mannan plays a role in neutrophil evasion by masking both glucan and chitin PAMPs.
“Cell wall mannan has also been shown to play a role in neutrophil evasion by masking both glucan and chitin PAMPs (21, 24).”
From Dual function of <i>Candida auris</i> mannosyltransferase, MNT5, in biofilm community protection from antifungal therapy and the host (2025) · cites this paper as [21]
The OBSERVATION section reports that C. auris evades human neutrophil engagement and killing. It does not show that cell-wall mannan causes this evasion or masks glucan and chitin PAMPs; searches for mannan, chitin, and cell-wall masking found no such finding in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredDifferences in mannan composition between C. auris and C. albicans contribute to decreased innate immune recognition, phagocytic activity, and clearance of C. auris in human neutrophils.
“Recent evidence indicates that differences in mannan composition between C. auris and C. albicans contribute to decreased innate immune recognition, phagocytic activity, and clearance of C. auris in human neutrophils (13, 27, 28).”
From Differential skin immune responses in mice intradermally infected with <i>Candida auris</i> and <i>Candida albicans</i> (2023) · cites this paper as [27]
The Observation section reports that human neutrophils engage and kill C. auris less effectively than C. albicans, supporting the differences in recognition, phagocytic engagement, and clearance. It does not establish that differences in mannan composition cause those effects; searches for mannan composition and mannose found no such comparison or causal finding in our copy. Page numbers were not available. (LLM, conf=0.90)
Experimental — accuracy not yet measuredC. auris exhibits remarkable resistance to neutrophil phagocytosis and killing ex vivo, unlike C. albicans, attributable to its unique cell wall composition.
“Unlike C. albicans, C. auris exhibits remarkable resistance to neutrophil phagocytosis and killing ex vivo, attributable to its unique cell wall composition [18,84].”
From Host–Candida auris interactions in the skin (2026) · cites this paper as [84]
The Observation section reports that human neutrophils engaged and killed C. auris far less effectively than C. albicans in coculture, supporting the ex vivo comparison. It does not establish that C. auris’s cell wall composition causes this resistance; searches for cell-wall composition and recognition found no such explanation in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredNeutrophils are less effective at engaging, phagocytosing, and killing C. auris when compared to C. albicans.
“However, neutrophils are less effective at engaging, phagocytosing, and killing C. auris when compared to C. albicans (21, 24).”
From Dual function of <i>Candida auris</i> mannosyltransferase, MNT5, in biofilm community protection from antifungal therapy and the host (2025) · cites this paper as [21]
Neutrophils are less efficient in recognizing and killing C. auris due to the presence of a dense mannan layer and recruit significantly fewer neutrophils than C. albicans in the murine infection.
“Recent evidence suggests that neutrophils are less efficient in recognizing and killing C. auris (29) due to the presence of a dense mannan layer (30) and recruit significantly fewer neutrophils than the C. albicans in the murine infection (5, 31).”
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 [29]
Primary human neutrophils show reduced phagocytosis and impaired NET formation against C. auris ex vivo compared to C. albicans.
“Johnson and colleagues reported that primary human neutrophils show reduced phagocytosis and impaired neutrophil extracellular trap (NET) formation against C. auris ex vivo compared to C. albicans [84].”
From Host–Candida auris interactions in the skin (2026) · cites this paper as [84]
In a zebrafish model of invasive candidiasis, neutrophil recruitment in vivo is reduced during C. auris compared to C. albicans infection.
“Using a zebrafish model of invasive candidiasis, reduced neutrophil recruitment in vivo was observed during C. auris compared to C. albicans infection [84].”
From Host–Candida auris interactions in the skin (2026) · cites this paper as [84]
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“However, neutrophils are less effective at engaging, phagocytosing, and killing C. auris when compared to C. albicans (21, 24).”
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- Authors
- Johnson, C. J., Davis, J. M., Huttenlocher, A., Kernien, J. F., & Nett, J. E.
- Affiliations
- University of Wisconsin–Madison (US)
- Department of Pediatrics, University of Wisconsin, Madison, Wisconsin, USA
- Corresponding author
- Nett, Jeniel E.
- Venue
- mBio
- Publisher
- American Society for Microbiology
- Published
- 2018-09-05
- Volume
- 9
- Issue
- 4
- ISSN
- 2150-7511 (ISSN-L)
- 2161-2129
- PMC
- PMC6106086
- OpenAlex
- W2888555021
- Cited by
- 157
- References
- 1
- Citations by year
- 2026: 25 · 2025: 18 · 2024: 23 · 2023: 21 · 2022: 20 · 2021: 13 · 2020: 22 · 2019: 11 · 2018: 4
- FWCI
- 9.46
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- mBio (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- HHS | National Institutes of Health (K08 AI108727, K08 AI132720)
- Burroughs Wellcome Fund (1012299)
- Doris Duke Charitable Foundation (112580130)
- Topics
- Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Keywords
- Candida auris, neutrophils, neutrophil extracellular traps, neutrophil recruitment, Candida albicans, invasive candidiasis, innate immune evasion, histones, zebrafish model, fungal virulence
- MeSH terms
- Animals, Candida, Candida albicans, Candidiasis, Humans, Immunity, Innate, Neutrophils, Virulence, Zebrafish, Coculture Techniques, Communicable Diseases, Emerging, Host-Pathogen Interactions, Immune Evasion, Extracellular Traps
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