Cecropin D-derived synthetic peptides in the fight against Candida albicans cell filamentation and biofilm formation

Abstract

The recent progressive increase in the incidence of invasive fungal infections, especially in immunocompromised patients, makes the search for new therapies crucial in the face of the growing drug resistance of prevalent nosocomial yeast strains. The latest research focuses on the active compounds of natural origin, inhibiting fungal growth, and preventing the formation of fungal biofilms. Antimicrobial peptides are currently the subject of numerous studies concerning effective antifungal therapy. In the present study, the antifungal properties of two synthetic peptides (ΔM3, ΔM4) derived from an insect antimicrobial peptide – cecropin D – were investigated. The fungicidal activity of both compounds was demonstrated against the yeast forms of Candida albicans, Candida tropicalis, and Candida parapsilosis, reaching a MFC99.9 in the micromolar range, while Candida glabrata showed greater resistance to these peptides. The scanning electron microscopy revealed a destabilization of the yeast cell walls upon treatment with both peptides; however, their effectiveness was strongly modified by the presence of salt or plasma in the yeast environment. The transition of C. albicans cells from yeast to filamentous form, as well as the formation of biofilms, was effectively reduced by ΔM4. Mature biofilm viability was inhibited by a higher concentration of this peptide and was accompanied by increased ROS production, activation of the GPX3 and SOD5 genes, and finally, increased membrane permeability. Furthermore, both peptides showed a synergistic effect with caspofungin in inhibiting the metabolic activity of C. albicans cells, and an additive effect was also observed for the mixtures of peptides with amphotericin B. The results indicate the possible potential of the tested peptides in the prevention and treatment of candidiasis.

Study of the Membrane Activity of the Synthetic Peptide ∆M3 Against Extended-Spectrum β-lactamase Escherichia coli Isolates

“…It is important to highlight that the spectroscopic assays were performed in dynamic environments at a certain temperature, buffer, and in the presence of a representative lipid system of E. coli and erythrocyte cell membrane. Nevertheless, the FT-IR result is not unexpected, in previous research the ΔM3 structural studies were performed by circular dichroism using 2,2,2-trifluoroethanol (TFE) concluding that the peptide was not susceptible to adopt a helical structure (Guevara-Lora et al 2023 ). Several peptides were demonstrated to be active without presenting a secondary structure.…”

“…Our research focuses on evaluating a synthetic cationic sequence called ΔM3, a cecropin D-derived peptide, against ESBL-producing E. coli isolates. We had previously reported the potential of this peptide against Staphylococcus aureus (Manrique-Moreno et al 2021 ), and its fungicide activity against the yeast forms of Candida albicans , Candida tropicalis , and Candida parapsilosis (Guevara-Lora et al 2023 ). Based on the activity of ΔM3, we decided to evaluate its potential antimicrobial and bactericidal activity against several ESBL-producing E. coli isolates.…”

A semi purified hydroalcoholic fraction from Caesalpinia bonduc seeds causes ergosterol biosynthesis inhibition in Candida albicans resulting in cell membrane damage

“…The prevalence and mortality rates of various fungal infections have elevated significantly in the last few years, especially candidiasis caused by Candida spp. ( Guevara-Lora et al, 2023 ). Although C. albicans is the most common pathogen responsible for candidiasis, nonalbicans Candida spp.…”

“…such as C. glabrata , C. krusei, C. dubliniensis, C. parapsilosis , and C. tropicalis are also major opportunistic fungal pathogens responsible for causing various hospital-associated infections. These pathogens are also a high risk for immunocompromised patients undergoing various surgeries or chemotherapy ( Guevara-Lora et al, 2023 ). C. albicans is a major opportunistic human pathogen that can reside in the oral cavity, intestinal tract, and vaginal area as a commensal microbiota.…”

Study of the Membrane Activity of the Synthetic Peptide ∆M3 against Extended-Spectrum β-Lactamase Escherichia coli Isolates

“…Our research focuses on evaluating a synthetic cationic sequence called DM3, a cecropin D-derived peptide, against ESBL-producing E. coli isolates. We had previously reported the potential of this peptide against Staphylococcus aureus (30), and its fungicide activity against the yeast forms of Candida albicans, Candida tropicalis, and Candida parapsilosis (13). Based on the activity of DM3, we decided to evaluate its potential antimicrobial and bactericidal activity against several ESBL-producing E. coli isolates.…”