Propranolol Ameliorates the Antifungal Activity of Azoles in Invasive Candidiasis

Author:

Mayandi Venkatesh12,Kang Wen-Tyng3,Ting Darren Shu Jeng145ORCID,Goh Eunice Tze Leng1,Lynn Myoe Naing6,Aung Thet Tun1ORCID,Vadivelu Jamuna3ORCID,Barathi Veluchamy Amutha27ORCID,Chan Anita Sook Yee278,Lakshminarayanan Rajamani129ORCID

Affiliation:

1. Ocular Infections and Anti-Microbials Research, Singapore Eye Research Institute, Singapore 169856, Singapore

2. Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Graduate Medical School, Singapore 169857, Singapore

3. Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Lembah Pantai, Kuala Lumpur 50603, Malaysia

4. Birmingham and Midland Eye Centre, Birmingham B18 7QH, UK

5. Academic Unit of Ophthalmology, Institute of Inflammation and Ageing, University of Birmingham, Birmingham B15 2TT, UK

6. Translational Ophthalmic Pathology-Immunology Platform, Singapore Eye Research Institute, Singapore 169856, Singapore

7. Translational Pre-Clinical Model Platform, Singapore Eye Research Institute, Singapore 169856, Singapore

8. Singapore National Eye Centre, Singapore 169856, Singapore

9. Department of Pharmacy, National University of Singapore, Singapore 117559, Singapore

Abstract

The effectiveness of current antifungal therapies is hampered by the emergence of drug resistance strains, highlighting an urgent need for new alternatives such as adjuvant antifungal treatments. This study aims to examine the synergism between propranolol and antifungal drugs, based on the premise that propranolol is known to inhibit fungal hyphae. In vitro studies demonstrate that propranolol potentiates the antifungal activity of azoles and that the effect is more pronounced for propranolol–itraconazole combination. Using an in vivo murine systemic candidemia model, we show that propranolol–itraconazole combination treatment resulted in a lower rate of body weight loss, decreased kidney fungal bioburden and renal inflammation when compared to propranolol and azole treatment alone or untreated control. Altogether, our findings suggest that propranolol increases the efficacy of azoles against C. albicans, offering a new therapeutic strategy against invasive fungal infections.

Funder

Singapore Ministry of Health’s National Medical Research Council

Open Funding—Independent Research Grant

SNEC Ophthalmic Technology Incubator Program

Publisher

MDPI AG

Subject

Pharmaceutical Science

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