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...

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Autores principales:	Chad J. Johnson, J. Muse Davis, Anna Huttenlocher, John F. Kernien, Jeniel E. Nett
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	Candida auris fungi immune neutrophil neutrophil extracellular trap zebrafish Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/70878f0764ff4321945cd7f286278314
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spelling	oai:doaj.org-article:70878f0764ff4321945cd7f2862783142021-11-15T16:00:16ZEmerging Fungal Pathogen <named-content content-type="genus-species">Candida auris</named-content> Evades Neutrophil Attack10.1128/mBio.01403-182150-7511https://doaj.org/article/70878f0764ff4321945cd7f2862783142018-09-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01403-18https://doaj.org/toc/2150-7511ABSTRACT 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.Chad J. JohnsonJ. Muse DavisAnna HuttenlocherJohn F. KernienJeniel E. NettAmerican Society for MicrobiologyarticleCandida aurisfungiimmuneneutrophilneutrophil extracellular trapzebrafishMicrobiologyQR1-502ENmBio, Vol 9, Iss 4 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Candida auris fungi immune neutrophil neutrophil extracellular trap zebrafish Microbiology QR1-502
spellingShingle	Candida auris fungi immune neutrophil neutrophil extracellular trap zebrafish Microbiology QR1-502 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
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.
format	article
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
title	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_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_sort	emerging fungal pathogen <named-content content-type="genus-species">candida auris</named-content> evades neutrophil attack
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/70878f0764ff4321945cd7f286278314
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Emerging Fungal Pathogen <named-content content-type="genus-species">Candida auris</named-content> Evades Neutrophil Attack

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