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.
Highlights
Candida albicans is an opportunistic yeast, responsible for systemic infections in individuals with impaired immune response [1]
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
The antibiofilm activity of hLF1-11 was evaluated against C. albicans reference strain SC5314 and on the clinical isolates (CA688, CA37, CA22) previously selected based on different RAPD profiles, propensity to produce biofilm, and fluconazole susceptibility (Table 1)
Summary
Candida albicans is an opportunistic yeast, responsible for systemic infections in individuals with impaired immune response [1]. Inhibition of Candida albicans Biofilm by hLF1-11 formation is a finely regulated process, which involves multiple interconnected signalling pathways [5], leading to a structured microbial community that is attached to a surface and embedded in an exopolymeric extracellular matrix [2,6,7]. The polysaccharide matrix acts as a barrier for sessile cells, preventing the entrance of most commonly used antifungal agents, conferring drug resistance. Thereby, biofilm is a reservoir of viable fungal cells potentially leading to systemic infections, with a mortality rate of 40–60% [10,11]
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