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Biofilm eradication and antifungal mechanism of action against Candida albicans of cationic dicephalic surfactants with a labile linker.

ABSTRACT: Our research aims to expand the knowledge on relationships between the structure of cationic dicephalic surfactants-N,N-bis[3,3_-(dimethylamine)propyl]alkylamide dihydrochlorides and N,N-bis[3,3_-(trimethylammonio)propyl]alkylamide dibromides (alkyl: n-C9H19, n-C11H23, n-C13H27, n-C15H31)-and their antifungal mechanism of action on Candida albicans. The mentioned groups of amphiphilic substances are characterized by the presence of a weak, hydrochloride cationic center readily undergoing deprotonation, as well as a stable, strong quaternary ammonium group and alkyl chains capable of strong interactions with fungal cells. Strong fungicidal properties and the role in creation and eradication of biofilm of those compounds were discussed in our earlier works, yet their mechanism of action remained unclear. It was shown that investigated surfactants induce strong oxidative stress and cause increase in cell membrane permeability without compromising its continuity, as indicated by increased potassium ion (K⁺) leakage. Thus experiments carried out on the investigated opportunistic pathogen indicate that the mechanism of action of the researched surfactants is different than in the case of the majority of known surfactants. Results presented in this paper significantly broaden the understanding on multifunctional cationic surfactants and their mechanism of action, as well as suggest their possible future applications as surface coating antiadhesives, fungicides and antibiofilm agents in medicine or industry.

SUBMITTER: Paluch E

PROVIDER: S-EPMC8076202 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Candida albicans, a ubiquitous opportunistic fungal pathogen, plays a pivotal role in human health and disease. As a commensal organism, it normally resides harmlessly within the human microbiota. However, under certain conditions, C. albicans can transition into a pathogenic state, leading to various infections collectively known as candidiasis. With the increasing prevalence of immunocompromised individuals and the widespread use of invasive medical procedures, candidiasis has become a significant public health concern. The emergence of drug-resistant strains further complicates treatment options, highlighting the urgent need for alternative therapeutic strategies. Antifungal peptides (AFPs) have gained considerable attention as potential candidates for combating Candida spp. infections. These naturally occurring peptides possess broad-spectrum antimicrobial activity, including specific efficacy against C. albicans. AFPs exhibit several advantageous properties, such as rapid killing kinetics, low propensity for resistance development, and diverse mechanisms of action, making them promising alternatives to conventional antifungal agents. In recent years, extensive research has focused on discovering and developing novel AFPs with improved efficacy and selectivity against Candida species. Advances in biotechnology and synthetic peptide design have enabled the modification and optimization of natural peptides, enhancing their stability, bioavailability, and therapeutic potential. Nevertheless, several challenges must be addressed before AFPs can be widely implemented in clinical practice. These include optimizing peptide stability, enhancing delivery methods, overcoming potential toxicity concerns, and conducting comprehensive preclinical and clinical studies. This commentary presents a short overview of candidemia and AFP; articles and reviews published in the last 10 years were searched on The National Library of Medicine (National Center for Biotechnology Information-NIH-PubMed). The terms used were C. albicans infections, antimicrobial peptides, antifungal peptides, antifungal peptides mechanisms of action, candidemia treatments and guidelines, synthetic peptides and their challenges, and antimicrobial peptides in clinical trials as the main ones. Older publications were cited if they brought some relevant concept or helped to bring a perspective into our narrative. Articles older than 20 years and those that appeared in PubMed but did not match our goal to bring updated information about using antifungal peptides as an alternative to C. albicans infections were not considered.

Project description:The antifungal activity of the 70% ethanol stem bark extract of Erythrina senegalensis (ESB) against different strains and drug resistant clinical isolates of Candida albicans and Candida glabrata were evaluated in the study. The effect of ESB on biofilms as well as its activity in combination with fluconazole, nystatin or caspofungin against the Candida strains were also evaluated. We then evaluated the antifungal activity of a microemulsion formulation of ESB against planktonic and biofilms of the Candida species. UPLC-QTOF-MS2 analysis was then undertaken to identify the phytoconstituents of the extract and UPLC fingerprints developed for the routine authentication as part of quality control measures. ESB exerted strong antifungal activities against C. albicans ATCC 10231 and SC5314 strains, and C. glabrata ATCC 2001 strain with minimum inhibitory concentration (MIC) values from 3.91 to 31.25 μg/mL and minimum fungicidal concentrations (MFCs) that ranged from 62.5 to 250 μg/mL. It also exhibited potent antifungal activities (MIC = 4–64 μg/mL) against a collection of C. albicans and C. glabrata clinical isolates that were resistant to either nystatin or azole antifungals. The formulated ESB demonstrated higher antifungal potency against the C. albicans and C. glabrata strains with MIC values of 3.91–31.25 μg/mL which was the same as the MFC values. The extract and its microemulsion formulation were active against biofilms of the strains of the Candida species inhibiting their biofilm formations (SMIC50 = 16–64 μg/mL) and their preformed biofilms (SMIC50 = 128 –>512 μg/mL). ESB also exhibited synergistic antifungal action with fluconazole and nystatin against C. albicans ATCC 10231 and C. glabrata ATCC 2001 strains in the checkerboard assay. Chemical characterization of the extract revealed the presence of phenolic compounds such as flavonoids and their prenylated derivatives, anthracene glycosides and alkaloids. UPLC Fingerprints of the extract was also developed and validated for routine identification and authentication of the stem bark of E. senegalensis. The study findings have demonstrated that the stem bark of E. senegalensis is as a potential source of bioactive compounds that could be developed as novel antifungal agents.

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Biofilm eradication and antifungal mechanism of action against Candida albicans of cationic dicephalic surfactants with a labile linker.

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