Giammarino Andrea, Bellucci Nicolò, Angiolella Letizia
Department of Public Health and Infectious Diseases, Sapienza University of Rome, Piazzale Aldo Moro 5, 00100 Rome, Italy.
Pathogens. 2024 Mar 7;13(3):233. doi: 10.3390/pathogens13030233.
The study of pathogenicity and virulence of fungal strains, in vivo in the preclinical phase, is carried out through the use of animal models belonging to various classes of mammals (rodents, leproids, etc.). Although animals are functionally more similar to humans, these studies have some limitations in terms of ethics (animal suffering), user-friendliness, cost-effectiveness, timing (physiological response time) and logistics (need for adequately equipped laboratories). A good in vivo model must possess some optimal characteristics to be used, such as rapid growth, small size and short life cycle. For this reason, insects, such as (Lepidoptera), (Diptera) and (Lepidoptera), have been widely used as alternative non-mammalian models. Due to their simplicity of use and low cost, the larvae of represent an optimal model above all to evaluate the virulence of fungal pathogens and the use of antifungal treatments (either single or in combination with biologically active compounds). A further advantage is also represented by their simple neuronal system limiting the suffering of the animal itself, their ability to survive at near-body ambient temperatures as well as the expression of proteins able to recognise combined pathogens following the three R principles (replacement, refinement and reduction). This review aims to assess the validity as well as the advantages and disadvantages of replacing mammalian classes with as an in vivo study model for preclinical experimentation.
在临床前阶段,通过使用属于各类哺乳动物(啮齿动物、灵长类动物等)的动物模型来开展真菌菌株致病性和毒力的体内研究。尽管动物在功能上与人类更为相似,但这些研究在伦理(动物痛苦)、用户友好性、成本效益、时间安排(生理反应时间)和后勤保障(需要配备完善的实验室)方面存在一些局限性。一个良好的体内模型必须具备一些可用于研究的最佳特性,例如生长迅速、体型小和生命周期短。因此,昆虫,如鳞翅目昆虫、双翅目昆虫和鳞翅目昆虫,已被广泛用作替代非哺乳动物模型。由于其使用简便且成本低廉,尤其是 的幼虫代表了一种评估真菌病原体毒力和抗真菌治疗(单一或与生物活性化合物联合使用)的最佳模型。其另一个优势还体现在它们简单的神经系统限制了动物自身的痛苦,它们在接近体温的环境温度下生存的能力以及遵循3R原则(替代、优化和减少)识别复合病原体的蛋白质表达。本综述旨在评估用 替代哺乳动物作为临床前实验体内研究模型的有效性以及优缺点。