Repurposing Pilocarpine Hydrochloride for Treatment of <named-content content-type="genus-species">Candida albicans</named-content> Infections

ABSTRACT Acetylcholine modulates the virulence of Candida albicans and regulates an appropriate immune response to infection in a Galleria mellonella infection model. Indeed, the evidence suggests that C. albicans possesses a functional cholinergic receptor that can regulate filamentous growth and b...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Christopher Nile, Monica Falleni, Daniela Cirasola, Abeer Alghamdi, Oliver F. Anderson, Christopher Delaney, Gordon Ramage, Emerenziana Ottaviano, Delfina Tosi, Gaetano Bulfamante, Giulia Morace, Elisa Borghi
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Candida albicans Galleria mellonella biofilm muscarinic pilocarpine hydrochloride repurposing Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/3f781b74dc9b49a396a7f1ff646169e3
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:3f781b74dc9b49a396a7f1ff646169e3
record_format	dspace
spelling	oai:doaj.org-article:3f781b74dc9b49a396a7f1ff646169e32021-11-15T15:22:04ZRepurposing Pilocarpine Hydrochloride for Treatment of <named-content content-type="genus-species">Candida albicans</named-content> Infections10.1128/mSphere.00689-182379-5042https://doaj.org/article/3f781b74dc9b49a396a7f1ff646169e32019-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00689-18https://doaj.org/toc/2379-5042ABSTRACT Acetylcholine modulates the virulence of Candida albicans and regulates an appropriate immune response to infection in a Galleria mellonella infection model. Indeed, the evidence suggests that C. albicans possesses a functional cholinergic receptor that can regulate filamentous growth and biofilm formation. Furthermore, G. mellonella immune cell subsets possess repertories of cholinergic receptors which regulate an effective and appropriate cellular immune response to C. albicans infection. This study aimed to investigate the cholinergic receptor subtype involved in regulation of filamentous growth and biofilm formation by C. albicans and determine the roles of cholinergic receptors in modulation of G. mellonella immune cell subsets. The general muscarinic receptor agonist, pilocarpine hydrochloride, inhibited C. albicans biofilm formation and pathogenicity, a phenomenon that could be reversed using the general muscarinic receptor antagonist, scopolamine. Pilocarpine hydrochloride protected G. mellonella larvae from C. albicans infection via inhibition of C. albicans filamentation and appropriate regulation of cellular immunity. However, scopolamine abrogated the capacity of pilocarpine hydrochloride to protect G. mellonella larvae from C. albicans infection. Furthermore, acetylcholine and pilocarpine hydrochloride exhibited differential modulatory capabilities on Galleria mellonella hemocyte responses to C. albicans. The data in this article demonstrate that a muscarinic receptor modulates C. albicans filamentation and biofilm formation. Furthermore, the results suggest that G. mellonella hemocyte subsets possess unique repertoires of cholinergic receptors that regulate their differentiation, activation, and function in contrasting manners. Therefore, targeting cholinergic receptors by repurposing currently licensed cholinergic drugs may offer novel therapeutic solutions for the prevention or treatment of fungal infections. IMPORTANCE Candida albicans is the most common human fungal pathogen with an estimated crude mortality rate of 40%. The ability of the organism to switch from the yeast to hyphal form and produce biofilms are important virulence factors. C. albicans infections are combatted by the host immune system. However, Candida triggers a strong inflammatory response that, if not appropriately regulated, can damage host tissues. Therefore, it is important that the host immune response eliminates the fungus but limits tissue damage. This study provides evidence that targeting cholinergic receptors cannot only curb the virulence of C. albicans by inhibiting filamentous growth and biofilm formation but can also appropriately regulate the host immune response to induce rapid clearance with limited damage to vital tissues. This article provides evidence that repurposing licensed drugs that target cholinergic receptors may offer novel therapeutic solutions for the prevention or treatment of fungal infections.Christopher NileMonica FalleniDaniela CirasolaAbeer AlghamdiOliver F. AndersonChristopher DelaneyGordon RamageEmerenziana OttavianoDelfina TosiGaetano BulfamanteGiulia MoraceElisa BorghiAmerican Society for MicrobiologyarticleCandida albicansGalleria mellonellabiofilmmuscarinicpilocarpine hydrochloriderepurposingMicrobiologyQR1-502ENmSphere, Vol 4, Iss 1 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Candida albicans Galleria mellonella biofilm muscarinic pilocarpine hydrochloride repurposing Microbiology QR1-502
spellingShingle	Candida albicans Galleria mellonella biofilm muscarinic pilocarpine hydrochloride repurposing Microbiology QR1-502 Christopher Nile Monica Falleni Daniela Cirasola Abeer Alghamdi Oliver F. Anderson Christopher Delaney Gordon Ramage Emerenziana Ottaviano Delfina Tosi Gaetano Bulfamante Giulia Morace Elisa Borghi Repurposing Pilocarpine Hydrochloride for Treatment of <named-content content-type="genus-species">Candida albicans</named-content> Infections
description	ABSTRACT Acetylcholine modulates the virulence of Candida albicans and regulates an appropriate immune response to infection in a Galleria mellonella infection model. Indeed, the evidence suggests that C. albicans possesses a functional cholinergic receptor that can regulate filamentous growth and biofilm formation. Furthermore, G. mellonella immune cell subsets possess repertories of cholinergic receptors which regulate an effective and appropriate cellular immune response to C. albicans infection. This study aimed to investigate the cholinergic receptor subtype involved in regulation of filamentous growth and biofilm formation by C. albicans and determine the roles of cholinergic receptors in modulation of G. mellonella immune cell subsets. The general muscarinic receptor agonist, pilocarpine hydrochloride, inhibited C. albicans biofilm formation and pathogenicity, a phenomenon that could be reversed using the general muscarinic receptor antagonist, scopolamine. Pilocarpine hydrochloride protected G. mellonella larvae from C. albicans infection via inhibition of C. albicans filamentation and appropriate regulation of cellular immunity. However, scopolamine abrogated the capacity of pilocarpine hydrochloride to protect G. mellonella larvae from C. albicans infection. Furthermore, acetylcholine and pilocarpine hydrochloride exhibited differential modulatory capabilities on Galleria mellonella hemocyte responses to C. albicans. The data in this article demonstrate that a muscarinic receptor modulates C. albicans filamentation and biofilm formation. Furthermore, the results suggest that G. mellonella hemocyte subsets possess unique repertoires of cholinergic receptors that regulate their differentiation, activation, and function in contrasting manners. Therefore, targeting cholinergic receptors by repurposing currently licensed cholinergic drugs may offer novel therapeutic solutions for the prevention or treatment of fungal infections. IMPORTANCE Candida albicans is the most common human fungal pathogen with an estimated crude mortality rate of 40%. The ability of the organism to switch from the yeast to hyphal form and produce biofilms are important virulence factors. C. albicans infections are combatted by the host immune system. However, Candida triggers a strong inflammatory response that, if not appropriately regulated, can damage host tissues. Therefore, it is important that the host immune response eliminates the fungus but limits tissue damage. This study provides evidence that targeting cholinergic receptors cannot only curb the virulence of C. albicans by inhibiting filamentous growth and biofilm formation but can also appropriately regulate the host immune response to induce rapid clearance with limited damage to vital tissues. This article provides evidence that repurposing licensed drugs that target cholinergic receptors may offer novel therapeutic solutions for the prevention or treatment of fungal infections.
format	article
author	Christopher Nile Monica Falleni Daniela Cirasola Abeer Alghamdi Oliver F. Anderson Christopher Delaney Gordon Ramage Emerenziana Ottaviano Delfina Tosi Gaetano Bulfamante Giulia Morace Elisa Borghi
author_facet	Christopher Nile Monica Falleni Daniela Cirasola Abeer Alghamdi Oliver F. Anderson Christopher Delaney Gordon Ramage Emerenziana Ottaviano Delfina Tosi Gaetano Bulfamante Giulia Morace Elisa Borghi
author_sort	Christopher Nile
title	Repurposing Pilocarpine Hydrochloride for Treatment of <named-content content-type="genus-species">Candida albicans</named-content> Infections
title_short	Repurposing Pilocarpine Hydrochloride for Treatment of <named-content content-type="genus-species">Candida albicans</named-content> Infections
title_full	Repurposing Pilocarpine Hydrochloride for Treatment of <named-content content-type="genus-species">Candida albicans</named-content> Infections
title_fullStr	Repurposing Pilocarpine Hydrochloride for Treatment of <named-content content-type="genus-species">Candida albicans</named-content> Infections
title_full_unstemmed	Repurposing Pilocarpine Hydrochloride for Treatment of <named-content content-type="genus-species">Candida albicans</named-content> Infections
title_sort	repurposing pilocarpine hydrochloride for treatment of <named-content content-type="genus-species">candida albicans</named-content> infections
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/3f781b74dc9b49a396a7f1ff646169e3
work_keys_str_mv	AT christophernile repurposingpilocarpinehydrochloridefortreatmentofnamedcontentcontenttypegenusspeciescandidaalbicansnamedcontentinfections AT monicafalleni repurposingpilocarpinehydrochloridefortreatmentofnamedcontentcontenttypegenusspeciescandidaalbicansnamedcontentinfections AT danielacirasola repurposingpilocarpinehydrochloridefortreatmentofnamedcontentcontenttypegenusspeciescandidaalbicansnamedcontentinfections AT abeeralghamdi repurposingpilocarpinehydrochloridefortreatmentofnamedcontentcontenttypegenusspeciescandidaalbicansnamedcontentinfections AT oliverfanderson repurposingpilocarpinehydrochloridefortreatmentofnamedcontentcontenttypegenusspeciescandidaalbicansnamedcontentinfections AT christopherdelaney repurposingpilocarpinehydrochloridefortreatmentofnamedcontentcontenttypegenusspeciescandidaalbicansnamedcontentinfections AT gordonramage repurposingpilocarpinehydrochloridefortreatmentofnamedcontentcontenttypegenusspeciescandidaalbicansnamedcontentinfections AT emerenzianaottaviano repurposingpilocarpinehydrochloridefortreatmentofnamedcontentcontenttypegenusspeciescandidaalbicansnamedcontentinfections AT delfinatosi repurposingpilocarpinehydrochloridefortreatmentofnamedcontentcontenttypegenusspeciescandidaalbicansnamedcontentinfections AT gaetanobulfamante repurposingpilocarpinehydrochloridefortreatmentofnamedcontentcontenttypegenusspeciescandidaalbicansnamedcontentinfections AT giuliamorace repurposingpilocarpinehydrochloridefortreatmentofnamedcontentcontenttypegenusspeciescandidaalbicansnamedcontentinfections AT elisaborghi repurposingpilocarpinehydrochloridefortreatmentofnamedcontentcontenttypegenusspeciescandidaalbicansnamedcontentinfections
_version_	1718428065876410368

Repurposing Pilocarpine Hydrochloride for Treatment of <named-content content-type="genus-species">Candida albicans</named-content> Infections

Ejemplares similares