Competitiveness during Dual-Species Biofilm Formation of Fusarium oxysporum and Candida albicans and a Novel Treatment Strategy

Abstract

During an infection, a single or multispecies biofilm can develop. Infections caused by non-dermatophyte molds, such as Fusarium spp. and yeasts, such as Candida spp., are particularly difficult to treat due to the formation of a mixed biofilm of the two species. Fusarium oxysporum is responsible for approximately 20% of human fusariosis, while Candida albicans is responsible for superficial mucosal and dermal infections and for disseminated bloodstream infections with a mortality rate above 40%. This study aims to investigate the interactions between C. albicans and F. oxysporum dual-species biofilm, considering variable formation conditions. Further, the ability of the WMR peptide, a modified version of myxinidin, to eradicate the mixed biofilm when used alone or in combination with fluconazole (FLC) was tested, and the efficacy of the combination of WMR and FLC at low doses was assessed, as well as its effect on the expression of some biofilm-related adhesin and hyphal regulatory genes. Finally, in order to confirm our findings in vivo and explore the synergistic effect of the two drugs, we utilized the Galleria mellonella infection model. We concluded that C. albicans negatively affects F. oxysporum growth in mixed biofilms. Combinatorial treatment by WMR and FLC significantly reduced the biomass and viability of both species in mature mixed biofilms, and these effects coincided with the reduced expression of biofilm-related genes in both fungi. Our results were confirmed in vivo since the synergistic antifungal activity of WMR and FLC increased the survival of infected larvae and reduced tissue invasion. These findings highlight the importance of drug combinations as an alternative treatment for C. albicans and F. oxysporum mixed biofilms.

VT-1161—A Tetrazole for Management of Mono- and Dual-Species Biofilms

“…Biofilms were grown in sterile flat-bottom 96-well microtiter test plates in TSB with or without 1% glucose for 24 h at 37 ◦C, as reported previously [ 16 ]. For the dual-species biofilm, the suspensions of the two microorganisms were prepared at a final concentration of 10 6 cells mL −1 (ratio 1:1), dispensed (100 μL per well), and incubated.…”

Unveiling the mechanism of action of acylated temporin L analogues against multidrug-resistant Candida albicans

“…The spread of Candida infections and the resistance issues to available antifungal drugs are rapidly increasing. In this scenario, AMPs represent a challenge to open novel avenues and hopes for overcoming the antifungal resistance 14 , 16 . Previously, using several synthetic strategies on some Temporin L derivatives, including lipidation strategy 29 we developed different analogues which exhibited strong ability to kill both Gram-positive and Gram-negative bacteria, and yeasts as Candida spp 21 .…”

“…Arg and Lys) while the hydrophobic residues determine their amphipathic conformation. Both the cationic nature and the secondary structure facilitate the interaction with the negatively charged membrane of microorganisms 12 , 13 , leading to insertion, destabilisation and disruption of the cell membrane, although they can also act on intracellular targets 14 , 15 . Since the cell membrane is the primary target of AMPs, microorganisms are less likely to develop a resistance mechanism, making AMPs promising drug candidates 16 .…”

Myxinidin-Derived Peptide against Biofilms Caused by Cystic Fibrosis Emerging Pathogens

“…The peptide WMR (NH 2 -WGIRRILKYGKRSK-CONH 2 ) is an AMP derived from the marine Myxinidin peptide and previously developed by Cantisani et al [ 52 ]. In previous studies, WMR showed a significant capacity both to inhibit and eradicate biofilms of P. aeruginosa and different Candida species [ 53 , 54 ]. Herein, to improve the proteolytic stability of WMR, we designed a series of five peptides and investigated their ability to inhibit and eradicate a five-species biofilm model comprising single- and dual-species biofilms of three emergent CF microorganisms ( C. albicans , S. maltophilia , A. xylosoxidans ).…”