<named-content content-type="genus-species">Candida auris</named-content> Phenotypic Heterogeneity Determines Pathogenicity <italic toggle="yes">In Vitro</italic>

ABSTRACT Candida auris is an enigmatic yeast that provides substantial global risk in health care facilities and intensive care units. A unique phenotype exhibited by certain isolates of C. auris is their ability to form small clusters of cells known as aggregates, which have been to a limited exten...

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Autores principales:	Jason L. Brown, Chris Delaney, Bryn Short, Mark C. Butcher, Emily McKloud, Craig Williams, Ryan Kean, Gordon Ramage
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	Candida auris aggregate host-pathogen interactions in vitro skin model heterogeneity Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/637757e2fbfa4088a4df06816f352e49
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spelling	oai:doaj.org-article:637757e2fbfa4088a4df06816f352e492021-11-15T15:30:15Z<named-content content-type="genus-species">Candida auris</named-content> Phenotypic Heterogeneity Determines Pathogenicity <italic toggle="yes">In Vitro</italic>10.1128/mSphere.00371-202379-5042https://doaj.org/article/637757e2fbfa4088a4df06816f352e492020-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00371-20https://doaj.org/toc/2379-5042ABSTRACT Candida auris is an enigmatic yeast that provides substantial global risk in health care facilities and intensive care units. A unique phenotype exhibited by certain isolates of C. auris is their ability to form small clusters of cells known as aggregates, which have been to a limited extent described in the context of pathogenic traits. In this study, we screened several nonaggregative and aggregative C. auris isolates for biofilm formation, where we observed a level of heterogeneity among the different phenotypes. Next, we utilized an RNA sequencing approach to investigate the transcriptional responses during biofilm formation of a nonaggregative and aggregative isolate of the initial pool. Observations from these analyses indicate unique transcriptional profiles in the two isolates, with several genes identified relating to proteins involved in adhesion and invasion of the host in other fungal species. From these findings, we investigated for the first time the fungal recognition and inflammatory responses of a three-dimensional skin epithelial model to these isolates. In these models, a wound was induced to mimic a portal of entry for C. auris. We show that both phenotypes elicited minimal response in the model minus induction of the wound, yet in the wounded tissue, both phenotypes induced a greater response, with the aggregative isolate more proinflammatory. This capacity of aggregative C. auris biofilms to generate such responses in the wounded skin highlights how this opportunistic yeast is a high risk within the intensive care environment where susceptible patients have multiple indwelling lines. IMPORTANCE Candida auris has recently emerged as an important cause of concern within health care environments due to its ability to persist and tolerate commonly used antiseptics and disinfectants, particularly when attached to a surface (biofilms). This yeast is able to colonize and subsequently infect patients, particularly those that are critically ill or immunosuppressed, which may result in death. We have undertaken analysis on two different phenotypic types of this yeast, using molecular and immunological tools to determine whether either of these has a greater ability to cause serious infections. We describe that both isolates exhibit largely different transcriptional profiles during biofilm development. Finally, we show that the inability to form small aggregates (or clusters) of cells has an adverse effect on the organism’s immunostimulatory properties, suggesting that the nonaggregative phenotype may exhibit a certain level of immune evasion.Jason L. BrownChris DelaneyBryn ShortMark C. ButcherEmily McKloudCraig WilliamsRyan KeanGordon RamageAmerican Society for MicrobiologyarticleCandida aurisaggregatehost-pathogen interactionsin vitro skin modelheterogeneityMicrobiologyQR1-502ENmSphere, Vol 5, Iss 3 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Candida auris aggregate host-pathogen interactions in vitro skin model heterogeneity Microbiology QR1-502
spellingShingle	Candida auris aggregate host-pathogen interactions in vitro skin model heterogeneity Microbiology QR1-502 Jason L. Brown Chris Delaney Bryn Short Mark C. Butcher Emily McKloud Craig Williams Ryan Kean Gordon Ramage <named-content content-type="genus-species">Candida auris</named-content> Phenotypic Heterogeneity Determines Pathogenicity <italic toggle="yes">In Vitro</italic>
description	ABSTRACT Candida auris is an enigmatic yeast that provides substantial global risk in health care facilities and intensive care units. A unique phenotype exhibited by certain isolates of C. auris is their ability to form small clusters of cells known as aggregates, which have been to a limited extent described in the context of pathogenic traits. In this study, we screened several nonaggregative and aggregative C. auris isolates for biofilm formation, where we observed a level of heterogeneity among the different phenotypes. Next, we utilized an RNA sequencing approach to investigate the transcriptional responses during biofilm formation of a nonaggregative and aggregative isolate of the initial pool. Observations from these analyses indicate unique transcriptional profiles in the two isolates, with several genes identified relating to proteins involved in adhesion and invasion of the host in other fungal species. From these findings, we investigated for the first time the fungal recognition and inflammatory responses of a three-dimensional skin epithelial model to these isolates. In these models, a wound was induced to mimic a portal of entry for C. auris. We show that both phenotypes elicited minimal response in the model minus induction of the wound, yet in the wounded tissue, both phenotypes induced a greater response, with the aggregative isolate more proinflammatory. This capacity of aggregative C. auris biofilms to generate such responses in the wounded skin highlights how this opportunistic yeast is a high risk within the intensive care environment where susceptible patients have multiple indwelling lines. IMPORTANCE Candida auris has recently emerged as an important cause of concern within health care environments due to its ability to persist and tolerate commonly used antiseptics and disinfectants, particularly when attached to a surface (biofilms). This yeast is able to colonize and subsequently infect patients, particularly those that are critically ill or immunosuppressed, which may result in death. We have undertaken analysis on two different phenotypic types of this yeast, using molecular and immunological tools to determine whether either of these has a greater ability to cause serious infections. We describe that both isolates exhibit largely different transcriptional profiles during biofilm development. Finally, we show that the inability to form small aggregates (or clusters) of cells has an adverse effect on the organism’s immunostimulatory properties, suggesting that the nonaggregative phenotype may exhibit a certain level of immune evasion.
format	article
author	Jason L. Brown Chris Delaney Bryn Short Mark C. Butcher Emily McKloud Craig Williams Ryan Kean Gordon Ramage
author_facet	Jason L. Brown Chris Delaney Bryn Short Mark C. Butcher Emily McKloud Craig Williams Ryan Kean Gordon Ramage
author_sort	Jason L. Brown
title	<named-content content-type="genus-species">Candida auris</named-content> Phenotypic Heterogeneity Determines Pathogenicity <italic toggle="yes">In Vitro</italic>
title_short	<named-content content-type="genus-species">Candida auris</named-content> Phenotypic Heterogeneity Determines Pathogenicity <italic toggle="yes">In Vitro</italic>
title_full	<named-content content-type="genus-species">Candida auris</named-content> Phenotypic Heterogeneity Determines Pathogenicity <italic toggle="yes">In Vitro</italic>
title_fullStr	<named-content content-type="genus-species">Candida auris</named-content> Phenotypic Heterogeneity Determines Pathogenicity <italic toggle="yes">In Vitro</italic>
title_full_unstemmed	<named-content content-type="genus-species">Candida auris</named-content> Phenotypic Heterogeneity Determines Pathogenicity <italic toggle="yes">In Vitro</italic>
title_sort	<named-content content-type="genus-species">candida auris</named-content> phenotypic heterogeneity determines pathogenicity <italic toggle="yes">in vitro</italic>
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/637757e2fbfa4088a4df06816f352e49
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<named-content content-type="genus-species">Candida auris</named-content> Phenotypic Heterogeneity Determines Pathogenicity <italic toggle="yes">In Vitro</italic>

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