Antifungal and Antibiofilm Activity of Cyclic Temporin L Peptide Analogues against Albicans and Non-Albicans Candida Species

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.

Antifungal Activity of the Frog Skin Peptide Temporin G and Its Effect on Candida albicans Virulence Factors

“…In recent years, the search for new therapeutic approaches with different targets or mechanisms of action has been constantly evolving [ 64 , 67 ], and several authors have proposed AMPs, and temporins, as promising scaffolds for the development of new antifungal compounds [ 13 , 14 , 16 , 23 , 24 , 25 , 68 ]. Our group and others have described the antifungal activity of temporins L and B [ 69 , 70 ]. A series of cyclic analogs of temporin L was tested against a panel of Candida species with MIC of 50 µM.…”

“…Furthermore, in comparison, some isoforms of temporin L were able to provoke an almost complete inhibition of biofilm formation and/or eradication at 25 µM. The same authors also hypothesized a local membrane permeabilization, with a type of carpet model, as the plausible mechanism of fungicidal activity [ 70 ]. Recently, a significant antifungal activity of temporin SHa analog was also observed, against a panel of yeasts and molds of clinical interest, with a synergistic effect when combined with amphotericin B [ 71 ].…”

Peptides to Overcome the Limitations of Current Anticancer and Antimicrobial Nanotherapies

“…The rigid structure of biofilms formed by extracellular polymeric substances (EPS) creates a barrier against the penetration of antimicrobial agents [121]. Most antimicrobial agents are designed to treat planktonic pathogens and result ineffective at treating biofilm infections [122,123]. The development of new therapeutic strategies against biofilms, especially for drug-resistant bacteria/fungi, is critically necessary.…”

Synthetic Amphipathic β-Sheet Temporin-Derived Peptide with Dual Antibacterial and Anti-Inflammatory Activities

“…We have particularly focused on Temporin L (TL, FVQWFSKFLGRIL), one of the most potent temporin isoforms but also the most highly hemolytic [ 35 ]. Indeed, our previous attempts were aimed at improving its biological profile through the application of several synthetic strategies, including proline decoration [ 36 ], lipidation, and side chain-to-side chain cyclizations [ 37 , 38 , 39 , 40 ]. Several TL analogues were developed and characterized through biophysical techniques to elucidate their mode of action, some of them also displayed a wide broad-spectrum antibacterial activity and no cytotoxicity on human cells.…”