Hyperexpression of CDRs and HWP1 genes negatively impacts on Candida albicans virulence.

C. albicans is a commensal organism present in the human microbiome of more than 60% of the healthy population. Transition from commensalism to invasive candidiasis may occur after a local or a general failure of host's immune system. This transition to a more virulent phenotype may reside eith...

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Autores principales:	Bruno Maras, Anna Maggiore, Giuseppina Mignogna, Maria D'Erme, Letizia Angiolella
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2f05486cf9f0427cb305a8506fe158b3
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spelling	oai:doaj.org-article:2f05486cf9f0427cb305a8506fe158b32021-12-02T20:11:10ZHyperexpression of CDRs and HWP1 genes negatively impacts on Candida albicans virulence.1932-620310.1371/journal.pone.0252555https://doaj.org/article/2f05486cf9f0427cb305a8506fe158b32021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0252555https://doaj.org/toc/1932-6203C. albicans is a commensal organism present in the human microbiome of more than 60% of the healthy population. Transition from commensalism to invasive candidiasis may occur after a local or a general failure of host's immune system. This transition to a more virulent phenotype may reside either on the capacity to form hyphae or on an acquired resistance to antifungal drugs. Indeed, overexpression of genes coding drug efflux pumps or adhesins, cell wall proteins facilitating the contact between the fungus and the host, usually marks the virulence profile of invasive Candida spp. In this paper, we compare virulence of two clinical isolates of C. albicans with that of laboratory-induced resistant strains by challenging G. mellonella larvae with these pathogens along with monitoring transcriptional profiles of drug efflux pumps genes CDR1, CDR2, MDR1 and the adhesin genes ALS1 and HWP1. Although both clinical isolates were found resistant to both fluconazole and micafungin they were found less virulent than laboratory-induced resistant strains. An unexpected behavior emerged for the former clinical isolate in which three genes, CDR1, CDR2 and HWP1, usually correlated with virulence, although hyperexpressed, conferred a less aggressive phenotype. On the contrary, in the other isolate, we observed a decreased expression of CDR1, CDR2 and HWP1as well as of MDR1 and ALS1 that may be consistent with the less aggressive performance observed in this strain. These altered gene expressions might directly influence Candida virulence or they might be an epiphenomenon of a vaster rearrangement occurred in these strains during the challenge with the host's environment. An in-deepth comprehension of this scenario could be crucial for developing interventions able to counteract C. albicans invasiveness and lethality.Bruno MarasAnna MaggioreGiuseppina MignognaMaria D'ErmeLetizia AngiolellaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 6, p e0252555 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Bruno Maras Anna Maggiore Giuseppina Mignogna Maria D'Erme Letizia Angiolella Hyperexpression of CDRs and HWP1 genes negatively impacts on Candida albicans virulence.
description	C. albicans is a commensal organism present in the human microbiome of more than 60% of the healthy population. Transition from commensalism to invasive candidiasis may occur after a local or a general failure of host's immune system. This transition to a more virulent phenotype may reside either on the capacity to form hyphae or on an acquired resistance to antifungal drugs. Indeed, overexpression of genes coding drug efflux pumps or adhesins, cell wall proteins facilitating the contact between the fungus and the host, usually marks the virulence profile of invasive Candida spp. In this paper, we compare virulence of two clinical isolates of C. albicans with that of laboratory-induced resistant strains by challenging G. mellonella larvae with these pathogens along with monitoring transcriptional profiles of drug efflux pumps genes CDR1, CDR2, MDR1 and the adhesin genes ALS1 and HWP1. Although both clinical isolates were found resistant to both fluconazole and micafungin they were found less virulent than laboratory-induced resistant strains. An unexpected behavior emerged for the former clinical isolate in which three genes, CDR1, CDR2 and HWP1, usually correlated with virulence, although hyperexpressed, conferred a less aggressive phenotype. On the contrary, in the other isolate, we observed a decreased expression of CDR1, CDR2 and HWP1as well as of MDR1 and ALS1 that may be consistent with the less aggressive performance observed in this strain. These altered gene expressions might directly influence Candida virulence or they might be an epiphenomenon of a vaster rearrangement occurred in these strains during the challenge with the host's environment. An in-deepth comprehension of this scenario could be crucial for developing interventions able to counteract C. albicans invasiveness and lethality.
format	article
author	Bruno Maras Anna Maggiore Giuseppina Mignogna Maria D'Erme Letizia Angiolella
author_facet	Bruno Maras Anna Maggiore Giuseppina Mignogna Maria D'Erme Letizia Angiolella
author_sort	Bruno Maras
title	Hyperexpression of CDRs and HWP1 genes negatively impacts on Candida albicans virulence.
title_short	Hyperexpression of CDRs and HWP1 genes negatively impacts on Candida albicans virulence.
title_full	Hyperexpression of CDRs and HWP1 genes negatively impacts on Candida albicans virulence.
title_fullStr	Hyperexpression of CDRs and HWP1 genes negatively impacts on Candida albicans virulence.
title_full_unstemmed	Hyperexpression of CDRs and HWP1 genes negatively impacts on Candida albicans virulence.
title_sort	hyperexpression of cdrs and hwp1 genes negatively impacts on candida albicans virulence.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/2f05486cf9f0427cb305a8506fe158b3
work_keys_str_mv	AT brunomaras hyperexpressionofcdrsandhwp1genesnegativelyimpactsoncandidaalbicansvirulence AT annamaggiore hyperexpressionofcdrsandhwp1genesnegativelyimpactsoncandidaalbicansvirulence AT giuseppinamignogna hyperexpressionofcdrsandhwp1genesnegativelyimpactsoncandidaalbicansvirulence AT mariaderme hyperexpressionofcdrsandhwp1genesnegativelyimpactsoncandidaalbicansvirulence AT letiziaangiolella hyperexpressionofcdrsandhwp1genesnegativelyimpactsoncandidaalbicansvirulence
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Hyperexpression of CDRs and HWP1 genes negatively impacts on Candida albicans virulence.

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