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Abstract

Infections caused by zygomycetes, which have been increasing in recent years, are known for their difficulty of diagnosis and treatment. Because little is known about this fungus and its infection, vigorous research is now in serious demand. As in many other systemic mycoses, animal model studies are essential in the investigation of zygomycosis, particularly for the study of pathogenesis, diagnosis and treatment. Unfortunately, such studies have been limited when compared with those of aspergillosis. To help investigating the disease, here in this review article, the profile of human zygomycosis is briefly described, followed by a review of the heretofore used animal models of zygomycosis. Among clinically important zygomycetes causing human infection, animal models are available for Absidia corymbifera, Rhizopus oryzae, R. microsporus var. rhizopodiformis, Rhizomucor pusillus and Cunninghamella bertholletiae. Mice are the most commonly used animals, but models using guinea pigs and rabbits are also available. Pretreatment of animals with cyclophosphamide, corticosteroid, alloxan or streptozocine is frequently done to create an immunocompromised state. Treatment with desferrioxamine, an iron chelator, is also used to make animal models. In terms of the route of infection, the airborne route is used for pathophysiological studies in pulmonary infection models, but sometimes intravenous injection is preferred, particularly for antifungal drug studies. When pathophysiological analysis is the purpose of the study, the animals must be cautiously examined both histopathologically and mycologically. For the most part, zygomycosis model studies can be performed in a similar manner to those of aspergillosis. However, Aspergillus spp. and zygomycetes are completely different fungi, and researchers should be aware of the specific, critical aspects when handling zygomycosis models, such as homogenization of infected organs and staining of pathological samples.

Robust Phagocyte Recruitment Controls the Opportunistic Fungal Pathogen Mucor circinelloides in Innate Granulomas In Vivo

“…Traditional animal models to study the pathogenesis of mucormycosis have been limited and do not allow for the integrative study of cellular interactions ( 13 ). Host expression studies of R. oryzae infections in the fruit fly ( Drosophila melanogaster ) infection model showed downregulation of genes in several pathways, including pathogen recognition, immune defense, and stress responses ( 14 ).…”

Ketoacidosis alone does not predispose to mucormycosis byLichtheimiain a murine pulmonary infection model

“…Murine models have been successfully used to study pathogenesis [10][11][12] and to evaluate therapy efficacy [13][14][15][16][17] of mucormycosis caused by Rhizopus and Mucor. Depending on the localization of mucormycosis to be studied, the route of infection differs; systemic infection via the tail vein to mimic hematogenous dissemination, 13,14,18 and pulmonary infections facilitated by intranasal or intratracheal application of spores are most commonly used.…”

Impairment of Th cell response in Card9 knockout mice with cutaneous mucormycosis caused by Rhizopus arrhizus

“…According to the published study, due to the few septa of zygomycetes, homogenizing with blades does not work for separating the viable fungi and may even break and kill the hyphae when done vigorously. [12] In our study, we used sterile glass homogenizers manually to homogenize the organs. The organs were homogenized to almost invisible tissue mass with the hyphae still alive.…”

“…Many animal model studies of zygomycosis were performed and the routes of infection included intravenous, intranasal, intrasinus, intraperitoneal and subcutaneous pathways . Although intravenous injection was the most common method in creating systemic infection due to its advantage of high reproducibility and easy technology, it was quite different from the clinical pathways of human mucormycosis and the targeted organs in systemic infections didn't overlap with the ones in human cases.…”