Abstract

Temporins are one of the largest families of antimicrobial peptides with both anti-inflammatory and antimicrobial activity. Herein, for a panel of cyclic temporin L isoform analogues, the antifungal and antibiofilm activities were determined against representative Candida strains, including C. albicans, C. glabrata, C. auris, C. parapsilosis and C. tropicalis. The outcomes indicated a significant anti-candida activity against planktonic and biofilm growth for four peptides (3, 7, 15 and 16). The absence of toxicity up to high concentrations and survival after infection were assessed in vivo by using Galleria mellonella larvae, and the correlation between conformation and cytotoxicity was investigated by fluorescence assays and circular dichroism (CD). By combining fluorescence spectroscopy, CD, dynamic light scattering, confocal and atomic force microscopy, the mode of action of four analogues was hypothesized. The results pinpointed that peptide 3 emerged as a non-toxic compound showing a potent antibiofilm activity and represents a promising compound for biomedical applications.

Highlights

  • Biofilms are aggregates of microorganisms or multicellular communities which embed themselves within a protective matrix of secreted extracellular polymeric substances, typically consisting of polysaccharides, proteins or peptides, lipids and DNA

  • C. albicans is the most common opportunistic pathogen, being endowed with a strong ability to switch from a yeast mode of growth to a hyphal morphology more adapted to the invasion of host tissues and able to form biofilms on abiotic and biotic surfaces, with increased recalcitrance and tolerance to existing antifungal agents [5–7]

  • DiscussionBiofilms are aggregates of microorganisms in which cells are embedded in a selfproduced matrix of extracellular polymeric substances (EPSs) that adhere to each other

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Summary

Introduction

Biofilms are aggregates of microorganisms or multicellular communities which embed themselves within a protective matrix of secreted extracellular polymeric substances, typically consisting of polysaccharides, proteins or peptides, lipids and DNA. Fungal biofilms are highly associated with persistent nosocomial infections, most commonly typical in immunocompromised patients due to constant contact with medical devices including catheters, cardiac pacemakers and prosthetic heart valves [1]. Candida [2], including C. albicans, C. auris, C. glabrata, C. parapsilosis and C. tropicalis [3], are responsible for fungal biofilm-associated infections in the hospital setting [4]. C. albicans is the most common opportunistic pathogen, being endowed with a strong ability to switch from a yeast mode of growth to a hyphal morphology more adapted to the invasion of host tissues and able to form biofilms on abiotic and biotic surfaces, with increased recalcitrance and tolerance to existing antifungal agents [5–7]. Other non-albicans Candida species such as Pharmaceutics 2022, 14, 454.

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