Repurposing Pilocarpine Hydrochloride for the treatment of Candida albicans infections

Nile, C. et al. (2019) Repurposing Pilocarpine Hydrochloride for the treatment of Candida albicans infections. mSphere, 4(1), e00689-18. (doi: 10.1128/mSphere.00689-18) (PMID:30674648) (PMCID:PMC6344604)

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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.

Item Type:Articles
Additional Information:Also supported by a Wellcome Trust Strategic Award for Medical Mycology and Fungal Immunology 097377/Z/11/Z grant awarded to GR.
Glasgow Author(s) Enlighten ID:Alghamdi, Abeer Muhammad A and Ramage, Professor Gordon and Delaney, Christopher and Nile, Dr Christopher
Authors: Nile, C., Falleni, M., Cirasola, D., Alghamdi, A., Anderson, O., Delaney, C., Ramage, G., Ottaviano, E., Tosi, D., Bulfamante, G., Morace, G., and Borghi, E.
College/School:College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Dental School
Journal Name:mSphere
Publisher:American Society for Microbiology
ISSN (Online):2379-5042
Copyright Holders:Copyright © 2019 The Authors
First Published:First published in mSphere 4(1):e00689-18
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
744671Understanding processes and mechanisms affecting the oral microbiome using OMICs approachesGordon RamageBiotechnology and Biological Sciences Research Council (BBSRC)BB/P504567/1SM - DENTAL SCHOOL