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Caractérisation de l’effet antifongique du composé d’origine végétale CIN-102 sur les champignons filamenteux septés et plus particulièrement Fusarium solani

Abstract : Today the increase of invasive fungal infections due to the rise of immunosuppressive therapies is a real problem especially in hospitals. Moreover, the emergence of resistant strains induces a therapeutic failure. Face to this issues, new classes of antifungals are expected. The plant kingdom thus represents an immense potential of natural resources to exploit for these purposes. The SEPTEOS company has recently developed the CIN-102 compound, by using cinnamaldehyde and potentiating compounds from two synergic essential oils of cinnamon. Cinnamaldehyde has already been describe to kill bacteria, yeast and molds growth in both growing and non-growing state (not published). The objective of this study is to determine the spectrum of activity of CIN-102 on the main genus or species of filamentous fungi involved in human pathology.The activity of CIN-102 product and its main constituent (cinnamaldehyde) are tested against a representative panel of strains of filamentous fungi (Aspergillus (n=40), Fusarium (n=20) and Scedosporium n=20)) of clinical importance. Clinical and reference strains have been studied, comprising isolates characterized by innate or acquired antifungal resistance patterns. A determination of MICs (minimum inhibitory concentrations) was performed using the M38-A2 CLSI reference method. The observed antifungal effect was then characterized by determining an inoculum effect. In a first part on the antifungal activity of CIN-102, we determined the minimum inhibitory concentration of the product for the different strains of the study with the CLSI method. The unimodal distribution of values shows the absence of resistance phenotype against our product. We also demonstrated the fungicidal effect of CIN-102 via a time kill assay, as well as its inhibitory effect on spore germination and on fungal growth and a post-antifungal effect similar to that of amphotericin B (treatment of first line of IFIs). Secondly, we studied the effect of CIN-102 in situations of resistance. We have demonstrated the lack of induced resistance of our product over several generations, unlike voriconazole (another first-line treatment for IFIs), as well as an inhibitory effect of the biofilm, an important virulence factor. The third part was to establish a mechanism of action of our product. We have already been able to demonstrate its impact on the plasma membrane and on the production of ROS, supplemented by a study in flow cytometry and genes involved in the reaction to CIN-102 have been demonstrated in a transcriptomic study.In conclusion, the inhibitory effects of our product on filamentous fungi, and the lack of resistance against it makes it an interesting candidate as a new antifungal. Further study including an in vivo study will be carried out in order to validate the potential of CIN-102 to offer new treatment possibilities against these pathologies very resistant to current antifungals and where mortality is too high.
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Submitted on : Thursday, April 7, 2022 - 12:05:47 PM
Last modification on : Friday, April 8, 2022 - 3:31:32 AM

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Maurine d'Agostino. Caractérisation de l’effet antifongique du composé d’origine végétale CIN-102 sur les champignons filamenteux septés et plus particulièrement Fusarium solani. Sciences du Vivant [q-bio]. Université de Lorraine, 2021. Français. ⟨NNT : 2021LORR0222⟩. ⟨tel-03633893⟩



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