Derivates of the Antifungal Peptide Cm-p5 Inhibit Development of Candida auris Biofilms In Vitro.

Dennis Kubiczek,Frank Rosenau,Heinz Raber,Melaine Gonzalez-García,Ludger Staendker,Fidel Morales-Vicente,Anselmo J Otero-Gonzalez

doi:10.3390/antibiotics9070363

Abstract

Growth in biofilms as a fascinating and complex microbial lifestyle has become widely accepted as one of the key features of pathogenic microbes, to successfully express their full virulence potential and environmental persistence. This also increases the threat posed by Candida auris, which has a high intrinsic ability to persist on abiotic surfaces including those of surgical instruments and medical tubing. In a previous study, cyclic and helical-stabilized analogues of the antifungal peptide Cm-p5 were designed and synthetized, and proved to have increased activities against C. albicans and C. parapsilosis, but not against planktonic C. auris cells cultivated in suspension cultures. Here, we demonstrate, initially, that these derivatives, however, exhibited semi-inhibitory concentrations between 10–21 µg/mL toward C. auris biofilms. Maturated biofilms were also arrested between 71–97%. These novel biofilm inhibitors may open urgently needed new routes for the development of novel drugs and treatments for the next stage of fight against C. auris.

Highlights

Compared to microbiological cultivation in laboratories, biofilms formed on biotic or abiotic surfaces are the most relevant and the “normal” lifestyle for microorganisms in general [1]
In a rational design study cyclic and helical-stabilized analogues of Cm-p5 were synthetized and proved increased activities against C. albicans and C. parapsilosis, but not against planktonic C. auris cells cultivated in suspension cultures
Candida auris was purchased from DSMZ (DSMZ-No 21092) and grown on YPD Agar (1% w/v yeast extract, 2% w/v peptone, 2% w/v glucose, 1.5% Agar)

Summary

Introduction

Compared to microbiological cultivation in laboratories, biofilms formed on biotic or abiotic surfaces are the most relevant and the “normal” lifestyle for microorganisms in general [1]. This is true for important pathogenic bacteria and lower eukaryotes. A special threat is that strains of C. auris with multiple resistances against commonly used antifungal drugs have been reported to occur independently in different countries/continents worldwide [9]. Both the U.S Center for Disease Control (CDC) and the European Centre for Disease Prevention and Control (ECDC) have released clinical alerts, initiating a broad public discourse, identifying C. auris as an emerging

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Results

Conclusion