Emerging Fungal Pathogen <named-content content-type="genus-species">Candida auris</named-content> Evades Neutrophil Attack
ABSTRACT 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 neutrop...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2018-09-01
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| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mBio.01403-18 |
| _version_ | 1818928382152278016 |
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| author | Chad J. Johnson J. Muse Davis Anna Huttenlocher John F. Kernien Jeniel E. Nett |
| author_facet | Chad J. Johnson J. Muse Davis Anna Huttenlocher John F. Kernien Jeniel E. Nett |
| author_sort | Chad J. Johnson |
| collection | DOAJ |
| description | ABSTRACT 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. |
| first_indexed | 2024-12-20T03:28:01Z |
| format | Article |
| id | doaj.art-70878f0764ff4321945cd7f286278314 |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-12-20T03:28:01Z |
| publishDate | 2018-09-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-70878f0764ff4321945cd7f2862783142022-12-21T19:55:03ZengAmerican Society for MicrobiologymBio2150-75112018-09-019410.1128/mBio.01403-18Emerging Fungal Pathogen <named-content content-type="genus-species">Candida auris</named-content> Evades Neutrophil AttackChad J. Johnson0J. Muse Davis1Anna Huttenlocher2John F. Kernien3Jeniel E. Nett4Department of Medicine, University of Wisconsin, Madison, Wisconsin, USADepartment of Pediatrics, University of Wisconsin, Madison, Wisconsin, USADepartment of Pediatrics, University of Wisconsin, Madison, Wisconsin, USADepartment of Medicine, University of Wisconsin, Madison, Wisconsin, USADepartment of Medicine, University of Wisconsin, Madison, Wisconsin, USAABSTRACT 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.https://journals.asm.org/doi/10.1128/mBio.01403-18Candida aurisfungiimmuneneutrophilneutrophil extracellular trapzebrafish |
| spellingShingle | Chad J. Johnson J. Muse Davis Anna Huttenlocher John F. Kernien Jeniel E. Nett Emerging Fungal Pathogen <named-content content-type="genus-species">Candida auris</named-content> Evades Neutrophil Attack mBio Candida auris fungi immune neutrophil neutrophil extracellular trap zebrafish |
| title | Emerging Fungal Pathogen <named-content content-type="genus-species">Candida auris</named-content> Evades Neutrophil Attack |
| title_full | Emerging Fungal Pathogen <named-content content-type="genus-species">Candida auris</named-content> Evades Neutrophil Attack |
| title_fullStr | Emerging Fungal Pathogen <named-content content-type="genus-species">Candida auris</named-content> Evades Neutrophil Attack |
| title_full_unstemmed | Emerging Fungal Pathogen <named-content content-type="genus-species">Candida auris</named-content> Evades Neutrophil Attack |
| title_short | Emerging Fungal Pathogen <named-content content-type="genus-species">Candida auris</named-content> Evades Neutrophil Attack |
| title_sort | emerging fungal pathogen named content content type genus species candida auris named content evades neutrophil attack |
| topic | Candida auris fungi immune neutrophil neutrophil extracellular trap zebrafish |
| url | https://journals.asm.org/doi/10.1128/mBio.01403-18 |
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