Experimental Mouse Models of Disseminated <named-content content-type="genus-species">Candida auris</named-content> Infection

ABSTRACT Disseminated candidiasis is a life-threatening disease and remains the most common bloodstream infection in hospitalized patients in the United States. Despite the availability of modern antifungal therapy, crude mortality in the last decade has remained unacceptably high. In particular, Ca...

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Autores principales:	Hong Xin, Farhan Mohiuddin, Jensen Tran, Abby Adams, Karen Eberle
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	disseminated candidiasis Candida auris neutrophil elastase (NE) complement Candida candidiasis Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/21bcdf67554c4f77a8fb4c733304363d
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spelling	oai:doaj.org-article:21bcdf67554c4f77a8fb4c733304363d2021-11-15T15:27:32ZExperimental Mouse Models of Disseminated <named-content content-type="genus-species">Candida auris</named-content> Infection10.1128/mSphere.00339-192379-5042https://doaj.org/article/21bcdf67554c4f77a8fb4c733304363d2019-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00339-19https://doaj.org/toc/2379-5042ABSTRACT Disseminated candidiasis is a life-threatening disease and remains the most common bloodstream infection in hospitalized patients in the United States. Despite the availability of modern antifungal therapy, crude mortality in the last decade has remained unacceptably high. In particular, Candida auris is a multidrug-resistant, health care-associated fungal pathogen and has recently emerged as the first fungal pathogen to cause a global public health threat. A reliable animal model for disseminated C. auris candidiasis is therefore needed to study the unique aspects of this little-known host-pathogen interaction. In this study, we established an inbred A/J intravenous model as an appropriate model for human disseminated C. auris infection. We found that C5 deficiency in A/J mice results in a complex phenotype characterized by rapid fungal proliferation in target organs and the development of a unique and rapidly fatal response. In contrast, C57BL/6J mice and mice deficient in neutrophil elastase (NE−/−) survived high-dose C. auris intravenous challenge, even with cyclophosphamide (CY)-induced immunosuppression. Our study is the first to provide insight into the role of C5 in the host responses to C. auris invasive infection and establishes an inbred A/J mouse model of systemic C. auris infection without CY-induced immunosuppression. IMPORTANCE In the last decade, Candida auris has emerged globally as a multidrug‐resistant fungal pathogen. Although C. auris was initially isolated from the external ear canal, it can cause outbreaks of invasive infections with very high mortality and comorbidities. Recent reports highlight the ongoing challenges due to organism misidentification, high rates of multifungal drug resistance, and unacceptably high patient mortality. The assessment of C. auris virulence in a specific genetic deficiency mouse model of invasive C. auris infection in this study contributes to the little knowledge of host defense to C. auris infection, which holds promise as a model for investigating the pathogenesis of C. auris invasive infection, exploring the immune responses elicited by the fungus, evaluating the possible induction of immunity to the infection, and targeting candidates for an antifungal vaccine.Hong XinFarhan MohiuddinJensen TranAbby AdamsKaren EberleAmerican Society for Microbiologyarticledisseminated candidiasisCandida aurisneutrophil elastase (NE)complementCandidacandidiasisMicrobiologyQR1-502ENmSphere, Vol 4, Iss 5 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	disseminated candidiasis Candida auris neutrophil elastase (NE) complement Candida candidiasis Microbiology QR1-502
spellingShingle	disseminated candidiasis Candida auris neutrophil elastase (NE) complement Candida candidiasis Microbiology QR1-502 Hong Xin Farhan Mohiuddin Jensen Tran Abby Adams Karen Eberle Experimental Mouse Models of Disseminated <named-content content-type="genus-species">Candida auris</named-content> Infection
description	ABSTRACT Disseminated candidiasis is a life-threatening disease and remains the most common bloodstream infection in hospitalized patients in the United States. Despite the availability of modern antifungal therapy, crude mortality in the last decade has remained unacceptably high. In particular, Candida auris is a multidrug-resistant, health care-associated fungal pathogen and has recently emerged as the first fungal pathogen to cause a global public health threat. A reliable animal model for disseminated C. auris candidiasis is therefore needed to study the unique aspects of this little-known host-pathogen interaction. In this study, we established an inbred A/J intravenous model as an appropriate model for human disseminated C. auris infection. We found that C5 deficiency in A/J mice results in a complex phenotype characterized by rapid fungal proliferation in target organs and the development of a unique and rapidly fatal response. In contrast, C57BL/6J mice and mice deficient in neutrophil elastase (NE−/−) survived high-dose C. auris intravenous challenge, even with cyclophosphamide (CY)-induced immunosuppression. Our study is the first to provide insight into the role of C5 in the host responses to C. auris invasive infection and establishes an inbred A/J mouse model of systemic C. auris infection without CY-induced immunosuppression. IMPORTANCE In the last decade, Candida auris has emerged globally as a multidrug‐resistant fungal pathogen. Although C. auris was initially isolated from the external ear canal, it can cause outbreaks of invasive infections with very high mortality and comorbidities. Recent reports highlight the ongoing challenges due to organism misidentification, high rates of multifungal drug resistance, and unacceptably high patient mortality. The assessment of C. auris virulence in a specific genetic deficiency mouse model of invasive C. auris infection in this study contributes to the little knowledge of host defense to C. auris infection, which holds promise as a model for investigating the pathogenesis of C. auris invasive infection, exploring the immune responses elicited by the fungus, evaluating the possible induction of immunity to the infection, and targeting candidates for an antifungal vaccine.
format	article
author	Hong Xin Farhan Mohiuddin Jensen Tran Abby Adams Karen Eberle
author_facet	Hong Xin Farhan Mohiuddin Jensen Tran Abby Adams Karen Eberle
author_sort	Hong Xin
title	Experimental Mouse Models of Disseminated <named-content content-type="genus-species">Candida auris</named-content> Infection
title_short	Experimental Mouse Models of Disseminated <named-content content-type="genus-species">Candida auris</named-content> Infection
title_full	Experimental Mouse Models of Disseminated <named-content content-type="genus-species">Candida auris</named-content> Infection
title_fullStr	Experimental Mouse Models of Disseminated <named-content content-type="genus-species">Candida auris</named-content> Infection
title_full_unstemmed	Experimental Mouse Models of Disseminated <named-content content-type="genus-species">Candida auris</named-content> Infection
title_sort	experimental mouse models of disseminated <named-content content-type="genus-species">candida auris</named-content> infection
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/21bcdf67554c4f77a8fb4c733304363d
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Experimental Mouse Models of Disseminated <named-content content-type="genus-species">Candida auris</named-content> Infection

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