title: Inhibition of Candida albicans Biofilm Formation by the Synthetic Lactoferricin Derived Peptide hLF1-11.
abstract: The aim of this study was to evaluate the in vitro activity of the synthetic peptide hLF1-11 against biofilm produced by clinical isolates of Candida albicans with different fluconazole susceptibility. The antibiofilm activity of the peptide hLF1-11 was assessed in terms of reduction of biofilm cellular density, metabolic activity and sessile cell viability. The extent of morphogenesis in hLF1-11 treated and untreated biofilms was also investigated microscopically. Transcription levels of genes related to cell adhesion, hyphal development and extracellular matrix production were analysed by qRT-PCR in hLF1-11 treated and untreated biofilms. Exogenous dibutyryl-cAMP (db-cAMP) was used to rescue morphogenesis in cells exposed to the peptide. The results revealed that hLF1-11 exhibited an inhibitory effect on biofilm formation by all C. albicans isolates tested in a dose-dependent manner, regardless of their fluconazole susceptibility. Visual inspection of treated or untreated biofilm cells with an inverted microscope revealed a significant reduction in hyphal formation by hLF1-11 treated cells, as early as 3 hours of incubation. Moreover, hLF1-11 showed a reduced activity on preadherent cells. hLF1-11 induced the down-regulation of biofilm and hyphal-associated genes, which were predominantly regulated via the Ras1-cAMP-Efg1 pathway. Indeed, exogenous db-cAMP restored morphogenesis in hLF1-11 treated cells. The hLF1-11 peptide significantly inhibited biofilm formation by C. albicans mainly at early stages, interfering with biofilm cellular density and metabolic activity, and affected morphogenesis through the Ras1-cAMP-Efg1 pathway. Our findings provide the first evidence that hLF1-11 could represent a potential candidate for the prevention of biofilm formation by C. albicans.
authors.affiliation: Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Morici
authors.affiliation: Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Fais
authors.affiliation: Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
authors.forename: Cosmeri
authors.initials: C
authors.lastname: Rizzato
authors.affiliation: Department of Biology, University of Pisa, Pisa, Italy.
authors.forename: Arianna
authors.initials: A
authors.lastname: Tavanti
authors.affiliation: Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy.
authors.forename: Antonella
authors.identifier: http://orcid.org/0000-0002-6975-8114
authors.initials: A
authors.lastname: Lupetti
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects*; D002176:Candida albicans / Q000166:cytology / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D002448:Cell Adhesion / Q000187:drug effects; D000242:Cyclic AMP / Q000494:pharmacology; D007781:Lactoferrin / Q000737:chemistry*; D009024:Morphogenesis / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D000935:Antifungal Agents; D010446:Peptide Fragments; C082171:lactoferricin B; D000242:Cyclic AMP; D007781:Lactoferrin