The synthetic killer peptide KP impairs Candida albicans biofilm in vitro.

Simona Paulone,Claudio Cermelli,Eva Pericolini,Walter Magliani,Samuele Peppoloni,Andrea Ardizzoni,Stefania Conti,Antonella Lupetti,Bruna Colombari,Serena Piccinelli,Elisabetta Blasi,Cosmeri Rizzato,Luciano Polonelli,Brunella Posteraro,Arianna Tavanti

doi:10.1371/journal.pone.0181278

Abstract

Candida albicans is a commensal organism, commonly inhabiting mucosal surfaces of healthy individuals, as a part of the resident microbiota. However, in susceptible hosts, especially hospitalized and/or immunocompromised patients, it may cause a wide range of infections. The presence of abiotic substrates, such as central venous or urinary catheters, provides an additional niche for Candida attachment and persistence, particularly via biofilm development. Furthermore, Candida biofilm is poorly susceptible to most antifungals, including azoles. Here we investigated the effects of a synthetic killer peptide (KP), known to be active in vitro, ex vivo and/or in vivo against different pathogens, on C. albicans biofilm. Together with a scrambled peptide used as a negative control, KP was tested against Candida biofilm at different stages of development. A reference strain, two fluconazole-resistant and two fluconazole-susceptible C. albicans clinical isolates were used. KP-induced C. albicans oxidative stress response and membrane permeability were also analysed. Moreover, the effect of KP on transcriptional profiles of C. albicans genes involved in different stages of biofilm development, such as cell adhesion, hyphal development and extracellular matrix production, was evaluated. Our results clearly show that the treatment with KP strongly affected the capacity of C. albicans to form biofilm and significantly impairs preformed mature biofilm. KP treatment resulted in an increase in C. albicans oxidative stress response and membrane permeability; also, biofilm-related genes expression was significantly reduced. Comparable inhibitory effects were observed in all the strains employed, irrespective of their resistance or susceptibility to fluconazole. Finally, KP-mediated inhibitory effects were observed also against a catheter-associated C. albicans biofilm. This study provides the first evidence on the KP effectiveness against C. albicans biofilm, suggesting that KP may be considered as a potential novel tool for treatment and prevention of biofilm-related C. albicans infections.

Highlights

Candida albicans is a commensal microorganism, commonly found in healthy individuals as a member of skin, gastrointestinal or vaginal microbiota
One of its most intriguing and poorly understood pathogenic peculiarities is its capability to organize in a biofilm on abiotic surfaces, such as implanted medical devices as well as on mucosal surfaces, including oral and vaginal epithelia [28]
We demonstrate that killer peptide (KP) is effective in preventing biofilm formation and that it significantly impairs an already structured C. albicans biofilm

Summary

Introduction

Candida albicans is a commensal microorganism, commonly found in healthy individuals as a member of skin, gastrointestinal or vaginal microbiota It becomes one of the major fungal pathogens in critically ill patients and immunocompromised individuals, where it causes severe, often life-threatening, deep-seated infections [1, 2]. This yeast has the capability to organize into structured microbial communities, known as biofilm, on abiotic (i.e. catheters and other medical devices) or biotic (i.e. oral mucosae) surfaces [3,4,5]. Antimicrobial peptides have recently been investigated as novel and potentially effective anti-biofilm compounds[10, 11]

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