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ZFIN ID: ZDB-PUB-180823-1
Emerging Fungal Pathogen Candida auris Evades Neutrophil Attack
Johnson, C.J., Davis, J.M., Huttenlocher, A., Kernien, J.F., Nett, J.E.
Date: 2018
Source: mBio   9(4): (Journal)
Registered Authors: Huttenlocher, Anna
Keywords: Candida auris, fungi, immune, neutrophil, neutrophil extracellular trap, zebrafish
MeSH Terms:
  • Animals
  • Candida/pathogenicity*
  • Candida albicans
  • Candidiasis/microbiology
  • Coculture Techniques
  • Communicable Diseases, Emerging/immunology
  • Communicable Diseases, Emerging/microbiology
  • Extracellular Traps/immunology
  • Host-Pathogen Interactions/immunology*
  • Humans
  • Immune Evasion*
  • Immunity, Innate
  • Neutrophils/immunology*
  • Neutrophils/microbiology
  • Virulence
  • Zebrafish/immunology
  • Zebrafish/microbiology
PubMed: 30131360 Full text @ MBio
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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.
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