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Repurposing pilocarpine hydrochloride for treatment of Candida albicans infections

Lookup NU author(s): Dr Christopher Nile

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2019 Nile et al. 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.


Publication metadata

Author(s): Nile C, Falleni M, Cirasola D, Alghamdi A, Anderson OF, Delaney C, Ramage G, Ottaviano E, Tosi D, Bulfamante G, Morace G, Borghi E

Publication type: Article

Publication status: Published

Journal: mSphere

Year: 2019

Volume: 4

Issue: 1

Online publication date: 23/01/2019

Acceptance date: 17/12/2018

Date deposited: 07/02/2020

ISSN (electronic): 2379-5042

Publisher: American Society for Microbiology

URL: https://doi.org/10.1128/mSphere.00689-18

DOI: 10.1128/mSphere.00689-18

PubMed id: 30674648


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