The synthetic killer peptide KP impairs Candida albicans biofilm in vitro

• Published in: PloS one 2017-07, Vol.12 (7), p.e0181278-e0181278
• Main Authors: Paulone, Simona, Ardizzoni, Andrea, Tavanti, Arianna, Piccinelli, Serena, Rizzato, Cosmeri, Lupetti, Antonella, Colombari, Bruna, Pericolini, Eva, Polonelli, Luciano, Magliani, Walter, Conti, Stefania, Posteraro, Brunella, Cermelli, Claudio, Blasi, Elisabetta, Peppoloni, Samuele
• Format: Article
• Language: English
• Subjects: Adhesion tests; Antifungal agents; Antifungal Agents - chemical synthesis; Antifungal Agents - pharmacology; Azoles; beta-Glucans - chemistry; beta-Glucans - immunology; Biofilms; Biofilms - drug effects; Biology and Life Sciences; Candida albicans; Candida albicans - drug effects; Candida albicans - physiology; Catheters; Cell adhesion; Cell Membrane - drug effects; Cell Membrane - metabolism; Clinical isolates; Control; Developmental stages; Extracellular matrix; Fluconazole; Fluconazole - pharmacology; Gene expression; Genes; Heterocyclic compounds; Immunocompromised hosts; In vitro methods and tests; Kinases; Medical instruments; Medical research; Medicine; Medicine and Health Sciences; Membrane permeability; Microbial growth; Microbial Sensitivity Tests; Mucosa; Oxidative stress; Oxidative Stress - drug effects; Peptides; Peptides - chemical synthesis; Peptides - pharmacology; Permeability; Permeability - drug effects; Public health; Research and Analysis Methods; Single-Chain Antibodies - chemistry; Single-Chain Antibodies - pharmacology; Substrates; Surface chemistry; Surgery; Testing; Transcription; Yeast
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0181278

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.