Journal article
Emerging Fungal Pathogen Candida auris Evades Neutrophil Attack
mBio, Vol.9(4), p.e01403-18
08/21/2018
DOI: 10.1128/mBio.01403-18
PMCID: PMC6106086
PMID: 30131360
Abstract
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
with neutrophils, leukocytes critical for control of invasive fungal infections. We show that human neutrophils do not effectively kill
Compared to
, neutrophils poorly recruited to
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
over
Imaging of neutrophils in a zebrafish larval model of invasive candidiasis revealed the recruitment of approximately 50% fewer neutrophils in response to
compared to
Upon encounter with
in the zebrafish hindbrain, neutrophils produced clouds of histones, suggesting the formation of NETs. These structures were not observed in
infection. Evasion of neutrophil attack and innate immunity offers an explanation for the virulence of this pathogen.
The emerging fungal pathogen
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
compared to the most commonly encountered
species,
While neutrophils produce neutrophil extracellular traps (NETs) upon encounter with
, these antimicrobial structures are not formed in response to
Using human neutrophils and a zebrafish model of invasive candidiasis, we show that
poorly recruits neutrophils and evades immune attack. Identification of this impaired innate immune response to
sheds light on the dismal outcomes for patients with invasive disease.
Details
- Title: Subtitle
- Emerging Fungal Pathogen Candida auris Evades Neutrophil Attack
- Creators
- Chad J Johnson - Department of Medicine, University of Wisconsin, Madison, Wisconsin, USAJ Muse Davis - Department of Pediatrics, University of Wisconsin, Madison, Wisconsin, USAAnna Huttenlocher - Department of Medical Microbiology and Immunology, University of Wisconsin, Madison, Wisconsin, USAJohn F Kernien - Department of Medicine, University of Wisconsin, Madison, Wisconsin, USAJeniel E Nett - Department of Medical Microbiology and Immunology, University of Wisconsin, Madison, Wisconsin, USA
- Resource Type
- Journal article
- Publication Details
- mBio, Vol.9(4), p.e01403-18
- DOI
- 10.1128/mBio.01403-18
- PMID
- 30131360
- PMCID
- PMC6106086
- NLM abbreviation
- mBio
- ISSN
- 2161-2129
- eISSN
- 2150-7511
- Grant note
- K08 AI132720 / NIAID NIH HHS K08 AI108727 / NIAID NIH HHS 2017074 / Doris Duke Charitable Foundation
- Language
- English
- Date published
- 08/21/2018
- Academic Unit
- Stead Family Department of Pediatrics; Infectious Disease (Pediatrics)
- Record Identifier
- 9984093508202771
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