Fungal infection models: Current progress ofex vivomethods

Abstract

| INTRODUC TI ONThe principles developed by Russell and Burch in 1959, concerning the use of animals in research, have been updated in recent decades, and cover the use of tissues from dead animals as alternatives to in vivo methods. 1 In vivo tests generally involve a large number of specimens to obtain representative results, and the well-being of these animals has become an ethical issue to be respected. 2 The term ex vivo refers to the use of living tissues, which are removed from an organism in vivo, for the application in experiments that will be performed in an artificial environment. 3The murine models used to evaluate the therapeutic profile of new antifungal agents are addressed in several studies, such as induction of keratitis, onychomycosis, and systemic, vaginal, pulmonary and cutaneous infections. 4-9 However, it is important to maintain a balance between qualified science and animal well-being, using rational and ethical ways of research. In this scenario, ex vivo models that simulate fungal infections in nails, mucous membranes and skin are promising alternatives that have been showing considerable results. [10][11][12] In order to demonstrate new perspectives in the evaluation of antifungal therapy, we will approach a critical review of the main ex vivo techniques used in the simulation and treatment of mycoses, providing an adaptation of the widely used in vivo methods. | ME THODS | Data source SummaryExperimental alternative ex vivo models that simulate infectious processes in vivo are of fundamental importance for the evaluation of new drugs, since in some cases, their execution does not depend on the approval of an ethics committee in research.Although studies using alternative infectious models to evaluate the efficacy of antifungal molecules have been increasingly described and reported, there is no critical consensus that establishes the most appropriate ones regarding the type of infection. Numerous studies contemplate ex vivo protocols of fungal infections on nails, corneas, dentinal tubules and skin and reveal counterpoints and concordances not yet finely confronted. In this minireview, we propose a critical analysis of the main ex vivo models of fungal infections for the evaluation of new antifungal candidates for both topical and systemic use, as opposed to the advantages and disadvantages of the traditional in vivo models employed in preclinical research. K E Y W O R D S dentinal tubule infections, ex vivo models, mucosal infections, onychomycosis, skin infection, systemic infections | 861 MACIEL QUATRIN ET AL. How to cite this article: Maciel Quatrin P, Flores Dalla Lana D, Andrzejewski Kaminski TF, Meneghello Fuentefria A. Fungal infection models: Current progress of ex vivo methods.

Four-Arm δ-Ornithine-Based Polypeptoids Resensitize Voriconazole against Azole-Resistant C. albicans

“…The in vivo efficacy of antifungals was examined using a mouse subcutaneous C. albicans infection model. , Immunosuppressed mice (KM, male) were infected by subcutaneous injection of 100 μL 1× 10 9 CFU/mL C. albicans on the back.…”

Optimization and Evaluation of Novel Antifungal Agents for the Treatment of Fungal Infection

“…Topical delivery of antifungal agents has been the traditional approach for fungal infections of the nails/toenails, corneas, mucous membranes, and skin. It has advantages such as low systemic toxicity, site-specific drug delivery, and better patient compliance. − Therefore, we next examined the in vivo antifungal efficacy of 22h for treating cutaneous or subcutaneous fungal infections using in vivo murine model. , When C. albicans was injected subcutaneously at the back of the shaved thigh, inflammation was induced within a day, which resulted in the sloughing off of the epidermal keratin layer (Figure A).…”

Ex vivo potential of a quinoline-derivative nail lacquer as a new alternative for dermatophytic onychomycosis treatment

“…The assay was performed in quadruplicate according to Quatrin et al . [32], with modifications.…”

“…Next, the suspended samples were diluted to 10 −3 , plated on SDA and incubated at 32 °C for 96 h. Finally, the total number of T. rubrum viable cells after exposure to the treatments was expressed as log 10 conidia/ml. The assay was performed in quadruplicate according to Quatrin et al [32], with modifications.…”