Global Transcriptomic Analysis of the <named-content content-type="genus-species">Candida albicans</named-content> Response to Treatment with a Novel Inhibitor of Filamentation

ABSTRACT The opportunistic pathogenic fungus Candida albicans can cause devastating infections in immunocompromised patients. Its ability to undergo a morphogenetic transition from yeast to filamentous forms allows it to penetrate tissues and damage tissues, and the expression of genes associated wi...

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Autores principales:	Jesus A. Romo, Hao Zhang, Hong Cai, David Kadosh, Julia R. Koehler, Stephen P. Saville, Yufeng Wang, Jose L. Lopez-Ribot
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Candida albicans candidiasis filamentation antivirulence Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/555a4c41abd14bd7900c3543726bc2d1
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spelling	oai:doaj.org-article:555a4c41abd14bd7900c3543726bc2d12021-11-15T15:27:33ZGlobal Transcriptomic Analysis of the <named-content content-type="genus-species">Candida albicans</named-content> Response to Treatment with a Novel Inhibitor of Filamentation10.1128/mSphere.00620-192379-5042https://doaj.org/article/555a4c41abd14bd7900c3543726bc2d12019-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00620-19https://doaj.org/toc/2379-5042ABSTRACT The opportunistic pathogenic fungus Candida albicans can cause devastating infections in immunocompromised patients. Its ability to undergo a morphogenetic transition from yeast to filamentous forms allows it to penetrate tissues and damage tissues, and the expression of genes associated with a number of pathogenetic mechanisms is also coordinately regulated with the yeast-to-hypha conversion. Therefore, it is widely considered that filamentation represents one of the main virulence factors of C. albicans. We have previously identified N-[3-(allyloxy)-phenyl]-4-methoxybenzamide (compound 9029936) as the lead compound in a series of small-molecule inhibitors of C. albicans filamentation and characterized its activity both in vitro and in vivo. This compound appears to be a promising candidate for the development of alternative antivirulence strategies for the treatment of C. albicans infections. In this study, we performed RNA sequencing analysis of samples obtained from C. albicans cells grown under filament-inducing conditions in the presence or absence of this compound. Overall, treatment with compound 9029936 resulted in 618 upregulated and 702 downregulated genes. Not surprisingly, some of the most downregulated genes included well-characterized genes associated with filamentation and virulence such as SAP5, ECE1 (candidalysin), and ALS3, as well as genes that impact metal chelation and utilization. Gene ontology analysis revealed an overrepresentation of cell adhesion, iron transport, filamentation, biofilm formation, and pathogenesis processes among the genes downregulated during treatment with this leading compound. Interestingly, the top upregulated genes suggested an enhancement of vesicular transport pathways, particularly those involving SNARE interactions. IMPORTANCE These results from whole-genome transcriptional profiling provide further insights into the biological activity and mode of action of a small-molecule inhibitor of C. albicans filamentation. This information will assist in the development of novel antivirulence strategies against C. albicans infections.Jesus A. RomoHao ZhangHong CaiDavid KadoshJulia R. KoehlerStephen P. SavilleYufeng WangJose L. Lopez-RibotAmerican Society for MicrobiologyarticleCandida albicanscandidiasisfilamentationantivirulenceMicrobiologyQR1-502ENmSphere, Vol 4, Iss 5 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Candida albicans candidiasis filamentation antivirulence Microbiology QR1-502
spellingShingle	Candida albicans candidiasis filamentation antivirulence Microbiology QR1-502 Jesus A. Romo Hao Zhang Hong Cai David Kadosh Julia R. Koehler Stephen P. Saville Yufeng Wang Jose L. Lopez-Ribot Global Transcriptomic Analysis of the <named-content content-type="genus-species">Candida albicans</named-content> Response to Treatment with a Novel Inhibitor of Filamentation
description	ABSTRACT The opportunistic pathogenic fungus Candida albicans can cause devastating infections in immunocompromised patients. Its ability to undergo a morphogenetic transition from yeast to filamentous forms allows it to penetrate tissues and damage tissues, and the expression of genes associated with a number of pathogenetic mechanisms is also coordinately regulated with the yeast-to-hypha conversion. Therefore, it is widely considered that filamentation represents one of the main virulence factors of C. albicans. We have previously identified N-[3-(allyloxy)-phenyl]-4-methoxybenzamide (compound 9029936) as the lead compound in a series of small-molecule inhibitors of C. albicans filamentation and characterized its activity both in vitro and in vivo. This compound appears to be a promising candidate for the development of alternative antivirulence strategies for the treatment of C. albicans infections. In this study, we performed RNA sequencing analysis of samples obtained from C. albicans cells grown under filament-inducing conditions in the presence or absence of this compound. Overall, treatment with compound 9029936 resulted in 618 upregulated and 702 downregulated genes. Not surprisingly, some of the most downregulated genes included well-characterized genes associated with filamentation and virulence such as SAP5, ECE1 (candidalysin), and ALS3, as well as genes that impact metal chelation and utilization. Gene ontology analysis revealed an overrepresentation of cell adhesion, iron transport, filamentation, biofilm formation, and pathogenesis processes among the genes downregulated during treatment with this leading compound. Interestingly, the top upregulated genes suggested an enhancement of vesicular transport pathways, particularly those involving SNARE interactions. IMPORTANCE These results from whole-genome transcriptional profiling provide further insights into the biological activity and mode of action of a small-molecule inhibitor of C. albicans filamentation. This information will assist in the development of novel antivirulence strategies against C. albicans infections.
format	article
author	Jesus A. Romo Hao Zhang Hong Cai David Kadosh Julia R. Koehler Stephen P. Saville Yufeng Wang Jose L. Lopez-Ribot
author_facet	Jesus A. Romo Hao Zhang Hong Cai David Kadosh Julia R. Koehler Stephen P. Saville Yufeng Wang Jose L. Lopez-Ribot
author_sort	Jesus A. Romo
title	Global Transcriptomic Analysis of the <named-content content-type="genus-species">Candida albicans</named-content> Response to Treatment with a Novel Inhibitor of Filamentation
title_short	Global Transcriptomic Analysis of the <named-content content-type="genus-species">Candida albicans</named-content> Response to Treatment with a Novel Inhibitor of Filamentation
title_full	Global Transcriptomic Analysis of the <named-content content-type="genus-species">Candida albicans</named-content> Response to Treatment with a Novel Inhibitor of Filamentation
title_fullStr	Global Transcriptomic Analysis of the <named-content content-type="genus-species">Candida albicans</named-content> Response to Treatment with a Novel Inhibitor of Filamentation
title_full_unstemmed	Global Transcriptomic Analysis of the <named-content content-type="genus-species">Candida albicans</named-content> Response to Treatment with a Novel Inhibitor of Filamentation
title_sort	global transcriptomic analysis of the <named-content content-type="genus-species">candida albicans</named-content> response to treatment with a novel inhibitor of filamentation
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/555a4c41abd14bd7900c3543726bc2d1
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Global Transcriptomic Analysis of the <named-content content-type="genus-species">Candida albicans</named-content> Response to Treatment with a Novel Inhibitor of Filamentation

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