Rimonabant potentiates the antifungal activity of amphotericin B by increasing cellular oxidative stress and cell membrane permeability

Zhang, Ming; Liang, Jinghui; Duan, Ximeng; Chen, Jinyao; Jin, Xueyang; Lin, Zhao‐Min; Pang, Yingxin; Wang, Xuexiang; Lou, Hongxiang; Chang, Wenqiang

doi:10.1093/femsyr/foab016

Cited by 9 publications

(4 citation statements)

References 39 publications

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“…It would be interesting to study whether SR141716A also has a direct anti-microbial effect. In this context, it is worth mentioning that SR141716A could potentiate the anti-fungal activity of amphotericin B against Candida albicans and Cryptococcus neoformans by increasing cellular oxidative stress and cell membrane permeability [434].…”

Section: The Relationship Between Gut Microbiota the Endocannabinoid ...mentioning

confidence: 99%

Anti-Microbial Activity of Phytocannabinoids and Endocannabinoids in the Light of Their Physiological and Pathophysiological Roles

Sionov

Steinberg

2022

Biomedicines

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Antibiotic resistance has become an increasing challenge in the treatment of various infectious diseases, especially those associated with biofilm formation on biotic and abiotic materials. There is an urgent need for new treatment protocols that can also target biofilm-embedded bacteria. Many secondary metabolites of plants possess anti-bacterial activities, and especially the phytocannabinoids of the Cannabis sativa L. varieties have reached a renaissance and attracted much attention for their anti-microbial and anti-biofilm activities at concentrations below the cytotoxic threshold on normal mammalian cells. Accordingly, many synthetic cannabinoids have been designed with the intention to increase the specificity and selectivity of the compounds. The structurally unrelated endocannabinoids have also been found to have anti-microbial and anti-biofilm activities. Recent data suggest for a mutual communication between the endocannabinoid system and the gut microbiota. The present review focuses on the anti-microbial activities of phytocannabinoids and endocannabinoids integrated with some selected issues of their many physiological and pharmacological activities.

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Section: The Relationship Between Gut Microbiota the Endocannabinoid ...mentioning

confidence: 99%

Anti-Microbial Activity of Phytocannabinoids and Endocannabinoids in the Light of Their Physiological and Pathophysiological Roles

Sionov

Steinberg

2022

Biomedicines

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“…Although the effects of AMPs on microorganisms are mainly attributed to their interaction with the cell membrane, other mechanisms have also been identified, including inhibition of cell wall biosynthesis or interaction with DNA (Buda De Cesare et al, 2020). However, certain peptides, such as salivary histatin 5 (Helmerhorst et al, 2001) or the venom wasp protonectin (Wang et al, 2015) involved also ROS production in their antifungal mechanism and induced oxidative stress in yeasts through uncontrolled accumulation of intracellular ROS, which led to cell apoptosis or necrosis (Kim et al, 2020;Seyedjavadi et al, 2020;Zhang et al, 2021). For ΔM3 and ΔM4 peptides, increased cell permeability was also accompanied by increased ROS production within the C. albicans biofilm, suggesting a more complex antifungal mechanism of peptide action.…”

Section: Discussionmentioning

confidence: 99%

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

Guevara-Lora

Bras²,

Juszczak³

et al. 2023

Front. Microbiol.

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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.

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“…The cell membrane permeability of C. albicans cells was assessed following previously established methods [47]. In brief, C. albicans cells that had been cultured overnight were prepared in a 10 mL solution of PBS at a concentration of 2 × 10 7 cells/mL.…”

Section: Cell Membrane Permeability Assaymentioning

confidence: 99%

Unexpected Inhibitory Effect of Octenidine Dihydrochloride on Candida albicans Filamentation by Impairing Ergosterol Biosynthesis and Disrupting Cell Membrane Integrity

Fang,

Xiong,

Wang

et al. 2023

Antibiotics

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Candida albicans filamentation plays a significant role in developing both mucosal and invasive candidiasis, making it a crucial virulence factor. Consequently, exploring and identifying inhibitors that impede fungal hyphal formation presents an intriguing approach toward antifungal strategies. In line with this anti-filamentation strategy, we conducted a comprehensive screening of a library of FDA-approved drugs to identify compounds that possess inhibitory properties against hyphal growth. The compound octenidine dihydrochloride (OCT) exhibits potent inhibition of hyphal growth in C. albicans across different hyphae-inducing media at concentrations below or equal to 3.125 μM. This remarkable inhibitory effect extends to biofilm formation and the disruption of mature biofilm. The mechanism underlying OCT’s inhibition of hyphal growth is likely attributed to its capacity to impede ergosterol biosynthesis and induce the generation of reactive oxygen species (ROS), compromising the integrity of the cell membrane. Furthermore, it has been observed that OCT demonstrates protective attributes against invasive candidiasis in Galleria mellonella larvae through its proficient eradication of C. albicans colonization in infected G. mellonella larvae by impeding hyphal formation. Although additional investigation is required to mitigate the toxicity of OCT in mammals, it possesses considerable promise as a potent filamentation inhibitor against invasive candidiasis.

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Rimonabant potentiates the antifungal activity of amphotericin B by increasing cellular oxidative stress and cell membrane permeability

Cited by 9 publications

References 39 publications

Anti-Microbial Activity of Phytocannabinoids and Endocannabinoids in the Light of Their Physiological and Pathophysiological Roles

Anti-Microbial Activity of Phytocannabinoids and Endocannabinoids in the Light of Their Physiological and Pathophysiological Roles

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

Unexpected Inhibitory Effect of Octenidine Dihydrochloride on Candida albicans Filamentation by Impairing Ergosterol Biosynthesis and Disrupting Cell Membrane Integrity

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