Antifungal and anti-biofilm effect of the calcium channel blocker verapamil on non-albicans Candida species.

Liliana Scorzoni,Evelyn Luzia De Souza Santos,Felipe De Camargo Ribeiro,José Benedito O Amorim,Priscila S Oliveira,Thais C Pereira,Luciane D De Oliveira,Luciana R.O Fugisaki,Raquel T De Menezes

doi:10.1590/0001-3765202020200703

Liliana Scorzoni, Evelyn Luzia De Souza Santos + Show 7 more

Open Access

https://doi.org/10.1590/0001-3765202020200703

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Abstract

Candida is a human fungal pathogen that causes a wide range of diseases. Candida albicans is the main etiologic agent in these diseases; however, infections can be caused by non-albicans Candida species. Virulence factors such as biofilm production, which protect the fungus from host immunity and anti-fungal drugs, are important for the infection. Therefore, available antifungal drugs for candidiasis treatment are limited and the investigation of new and effective drugs is needed. Verapamil is a calcium channel blocker with an inhibitory effect on hyphae development, adhesion, and colonization of C. albicans. In this study, we investigated the effect of verapamil on cell viability and its antifungal and anti-biofilm activity in non-albicans Candida species. Verapamil was not toxic to keratinocyte cells; moreover, C. krusei, C. parapsilosis, and C. glabrata were susceptible to verapamil with a minimal inhibitory concentration (MIC) of 1250 μM; in addition, this drug displayed fungistatic effect at the evaluated concentrations. After treatment with verapamil, reduced viability, biomass, and mitochondrial activity were observed in biofilms of the non-albicans Candida species C. krusei, C. glabrata, and C. parapsilosis. These findings highlight the importance of the study of verapamil as an alternative treatment for infections caused by non-albicans Candida species.

Highlights

In the last decade, an increase in the incidence of Candida spp. infections was observed; this was found to be associated with an increase in the number of immunocompromised patients (Quindós et al 2018, Salehi et al 2019, Walsh et al 2019)
Susceptibility of non-albicans Candida species to verapamil The evaluation of the antifungal activity of verapamil showed that this drug was active against C. krusei, C. parapsilosis, and C. glabrata with a minimal inhibitory concentration (MIC) of 1250 μM
An MCF assay demonstrated that verapamil displayed fungistatic activity at the evaluated concentration, able to growth in all evaluated concentrations (Table I)

Summary

INTRODUCTION

An increase in the incidence of Candida spp. infections was observed; this was found to be associated with an increase in the number of immunocompromised patients (Quindós et al 2018, Salehi et al 2019, Walsh et al 2019). VERAPAMIL EFFECT ON CANDIDA NON-albicans SPECIES prostheses, and possessing a compromised immune system are risk factors for the production of a microenvironment that favors the overgrowth of Candida spp. This may trigger oral candidiasis, which is the most prevalent opportunistic fungal infection affecting the oral mucosa (Singh et al 2014). Matrix components like exopolymers hinder the diffusion of drugs into the cells of the biofilm by binding to them, making the fungi refractory to antifungals (Al-Fattani & Douglas 2004, Dominguez et al 2018, Rodrigues et al 2017) This property of biofilms leads to persistent biofilm infections, despite treatment with antibiotics, predisposing the organism to develop resistance against these drugs (genetic resistance) (Ciofu et al 2017). In this study, we evaluated the antifungal activity of verapamil against non-albicans Candida species as well as the effect of verapamil on biofilm formation

MATERIALS AND METHODS

RESULTS

DISCUSSION