Repurposing Pilocarpine Hydrochloride for Treatment of Candida albicans Infections

Author:

Nile Christopher1,Falleni Monica2,Cirasola Daniela3,Alghamdi Abeer1,Anderson Oliver F.1,Delaney Christopher1,Ramage Gordon1,Ottaviano Emerenziana3,Tosi Delfina2,Bulfamante Gaetano2,Morace Giulia3,Borghi Elisa3

Affiliation:

1. Oral Sciences Research Group, University of Glasgow Dental School, School of Medicine, Dentistry and Nursing, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom

2. Division of Human Pathology, Department of Health Sciences, Università degli Studi di Milano, Milan, Italy

3. Laboratory of Microbiology, Department of Health Sciences, Università degli Studi di Milano, Milan, Italy

Abstract

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.

Funder

Universita degli studi di Milano-Linea B

BBSRC Industrial CASE

Wellcome Trust

Publisher

American Society for Microbiology

Subject

Molecular Biology,Microbiology

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