Benzamil Hydrochloride Has Antifungal Activity Against Candida albicans Biofilms In Vitro

Ref ID: 18726

Author:

M. Jahng, PharmD – Infectious Diseases Pharmacist1, H. S. Rane, BS – Research Assistant 1,2, S. M. Bernardo, PhD – Post Doctoral Research Fellow 1,2, S. A. Lee, MD, PhD – Section Chief, Infectious Diseases 1,2;

Author address:

1New Mexico VA Healthcare System, Albuquerque, NM, 2Univ. of New Mexico, Albuquerque, NM.

Full conference title:

52nd Annual ICAAC

Date: 9 September 2014

Abstract:

Background: There are only 3 major classes of systemic antifungal drugs, and morbidity and attributable mortality due to invasive candidiasis remains unacceptably high. In a high throughput screen of the Prestwick Chemical Library against specific C. albicans drug targets, benzamil HCl (BENZ) was identified as a lead compound. Benzamil HCl is a derivative of amiloride, a potassium sparing diuretic, and is an inhibitor of Na+/H+ and Na+/Ca++ channels. In this study, we sought to characterize the in vitro antifungal activity of BENZ against mature biofilms formed by C. albicans and the effect of BENZ on planktonic cells’ ability to form biofilms. Methods: Candida albicans wild-type reference strain SC5314 was used in all experiments. For treatment, mature biofilms were incubated for 24 hours with RPMI containing serial dilutions of BENZ. Metabolic activity of the biofilms was assessed using XTT-reduction assay. For prevention, C. albicans planktonic cells were seeded in RPMI containing serial dilutions of BENZ. After 24 hours, the resulting biofilms were analyzed using XTT-reduction assay and phase contrast light microscopy. The degree of metabolic inhibition was expressed as a percentage of the treated wells relative to the untreated control wells. Results: Statistically significant reduction of metabolic activity of the C. albicans biofilms treated with high concentrations of BENZ was seen. At BENZ concentrations of 2048, 1024, 512, and 256 μg/mL, metabolic activity was reduced by 87, 81.4, 61.1, and 25.8%, respectively. Complete prevention of biofilm formation was observed at concentrations 2048 and 1024 μg/mL. Metabolic activity of the resulting biofilms formed in the presence of BENZ 512 and 256 μg/mL was reduced by 54.9 and 28.1%, respectively. Biofilms formed in the presence of high doses of BENZ were dramatically sparse when visualized by microscopy. Conclusions: High concentrations of BENZ were highly active against mature C. albicans biofilms and prevented biofilm formation in vitro. Further studies of BENZ as a potential option in the treatment of C. albicans infections are warranted.

Abstract Number: F-2000

Conference Year: 2012

Link to conference website: NULL

New link: NULL

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