Optimum Inhibition of Amphotericin-B-Resistant Candida albicans Strain in Single- and Mixed-Species Biofilms by Candida and Non-Candida Terpenoids.

Hidaya F. Z. Touil,Zahia Boucherit-Otmani,Sameh S. M. Soliman,Ghalia Kohder,Kebir Boucherit,Mohamed Madkour

doi:10.3390/biom10020342

Hidaya F. Z. Touil, Zahia Boucherit-Otmani + Show 4 more

Open Access

https://doi.org/10.3390/biom10020342

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Abstract

Candida albicans is one of the most common human fungal pathogens and represents the most important cause of opportunistic mycoses worldwide. Surgical devices including catheters are easily contaminated with C. albicans via its formation of drug-resistant biofilms. In this study, amphotericin-B-resistant C. albicans strains were isolated from surgical devices at an intensive care center. The objective of this study was to develop optimized effective inhibitory treatment of resistant C. albicans by terpenoids, known to be produced naturally as protective signals. Endogenously produced farnesol by C. albicans yeast and plant terpenoids, carvacrol, and cuminaldehyde were tested separately or in combination on amphotericin-B-resistant C. albicans in either single- or mixed-infections. The results showed that farnesol did not inhibit hyphae formation when associated with bacteria. Carvacrol and cuminaldehyde showed variable inhibitory effects on C. albicans yeast compared to hyphae formation. A combination of farnesol with carvacrol showed synergistic inhibitory activities not only on C. albicans yeast and hyphae, but also on biofilms formed from single- and mixed-species and at reduced doses. The combined terpenoids also showed biofilm-penetration capability. The aforementioned terpenoid combination will not only be useful in the treatment of different resistant Candida forms, but also in the safe prevention of biofilm formation.

Highlights

Candida albicans is the fourth most common cause of nosocomial bloodstream infection [1,2]
Our recent data indicated that the Minimum Inhibitory Concentration (MIC) of amphotericin B for the planktonic forms of C. albicans clinical isolates ranges between 0.25–1 μg/mL, and the biofilm formed from all tested strains showed resistance to amphotericin B [18]
High concentrations up to 32 and 64 μg/mL of amphotericin B were required to inhibit the single-species biofilms formed by C. albicans A5 and A6 strains [18], compared to 4 μg/mL required to inhibit the biofilm formed by ATCC10231 strain

Summary

Introduction

Candida albicans is the fourth most common cause of nosocomial bloodstream infection [1,2]. C. albicans infections are common among hospital patients and elderly people, and are difficult to control [3]. About 50% of adult people have C. albicans yeasts in their mouths, and it is responsible for superficial, treated infections. C. albicans infections can spread throughout the body and become life-threatening, with immune-compromised patients [4]. C. albicans infections are very difficult to treat due to their resistance to antifungal drugs, expression of virulence factors, and ability to form biofilms. C. albicans can switch between two forms, the yeast and hyphae forms. The switch from yeast to hyphae is a recognized virulence factor of C. albicans [6], since it is mainly associated with drug-resistant biofilm formation. Most candidiases are associated with the formation of biofilms at a wide range of implanted medical devices [7]

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