The Antimicrobial Peptide AMP-17 Derived from Musca domestica Inhibits Biofilm Formation and Eradicates Mature Biofilm in Candida albicans

Abstract

The biofilm formation of C. albicans represents a major virulence factor during candidiasis. Biofilm-mediated drug resistance has necessitated the search for a new antifungal treatment strategy. In our previous study, a novel antimicrobial peptide named AMP-17 derived from Musca domestica was confirmed to have significant antifungal activity and suppress hyphal growth greatly in C. albicans. In the current work, we aimed to investigate the antibiofilm property of AMP-17 in C. albicans and explore the underlying mechanism. An antifungal susceptibility assay showed that AMP-17 exerted a strong inhibitory efficacy on both biofilm formation and preformed biofilms in C. albicans. Furthermore, AMP-17 was found to block the yeast-to-hypha transition and inhibit the adhesion of biofilm cells with a reduction in cellular surface hydrophobicity. A morphological analysis revealed that AMP-17 indeed suppressed typical biofilm formation and damaged the structures of the preformed biofilm. The RNA-seq showed that the MAPK pathway, biosynthesis of antibiotics, and essential components of the cell were mainly enriched in the biofilm-forming stage, while the citrate cycle (TCA cycle), phenylamine metabolism, and propanoate metabolism were enriched after the biofilm matured. Moreover, the co-expressed DEGs in the two pairwise comparisons highlighted the terms of transmembrane transporter activity, regulation of filamentation, and biofilm formation as important roles in the antibiofilm effect of AMP-17. Additionally, qRT-PCR confirmed that the level of the genes involved in cell adhesion, filamentous growth, MAPK, biofilm matrix, and cell dispersal was correspondingly altered after AMP-17 treatment. Overall, our findings reveal the underlying antibiofilm mechanisms of AMPs in C. albicans, providing an interesting perspective for the development of effective antifungal agents with antibiofilm efficacy in Candida spp.

Combined Use of Antimicrobial Peptides with Antiseptics against Multidrug-Resistant Bacteria: Pros and Cons

“…These results can be taken with a sufficient optimism regarding the potential of AMP/antiseptic implementation in coatings of medical devices, routine care products, or acute wound treatment. At the same time, literature data [ 22 , 125 , 126 ] suggest that eradicating well-established biofilms can require an order of magnitude higher concentrations of AMPs than the ones needed for the prophylactic against their formation or require prolonged exposure [ 127 ]. Thus, to properly assess the prospects of combined use of AMPs and antiseptics against such challenges, additional testing on preformed biofilms will be important.…”

Mar1, an HMG-box protein, regulatesn-alkane adsorption and cell morphology of the dimorphic yeastYarrowia lipolytica

“…In fact, it has been demonstrated that cell surface hydrophobicity is altered by filamentation in Candida tropicalis (50). Several drugs have also been reported to reduce cell surface hydrophobicity and inhibit filamentous growth in C. albicans (51)(52)(53)(54)(55)(56)(57)(58)(59)(60). Therefore, it is possible that there exist mechanisms that simultaneously regulate cell surface hydrophobicity and cell morphology in dimorphic yeasts and that Mar1 is involved in their regulation in Y.…”

Antibiofilm Activity and Biocompatibility of Temporin-SHa: A Promising Antimicrobial Peptide for Control of Fluconazole-Resistant Candida albicans

“…The action of other AMP classes to control C. albicans biofilm has been observed in the literature. AMP-17 peptide showed strong efficacy in C. albicans (SC 5314), inhibiting 86% of mature biofilm [ 43 ]. Additionally, the gH625-M membranotropic peptide showed efficacy, inhibiting 52% of persistently derived C. albicans (ATCC 90028) by targeting the structure of the cell membrane [ 44 ].…”