Santos Fabiola, Nequiz Mario, Hernández-Cuevas Nora Adriana, Hernández Kahory, Pineda Erika, Encalada Rusely, Guillén Nancy, Luis-García Erika, Saralegui Andrés, Saavedra Emma, Pérez-Tamayo Ruy, Olivos-García Alfonso
Departamento de Medicina Experimental, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico, D.F. 04510, Mexico.
Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, México, D.F. 11340, Mexico.
Cell Microbiol. 2015 Jul;17(7):1037-51. doi: 10.1111/cmi.12419. Epub 2015 Feb 18.
Adhesion to cells, cytotoxicity and proteolysis are functions required for virulence and pathogenicity of Entamoeba histolytica. However, there was no correlation between these in vitro functions and the early elimination of non-pathogenic E. dispar and non-virulent E. histolytica (nvEh) in experimental amoebic liver abscesses developed in hamsters. Thus, additional functions may be involved in amoebic pathogenicity and virulence. In the present study, an integral experimental assessment, including innovative technologies for analyses of amoebal pathophysiology, cell biology, biochemistry and transcriptomics, was carried out to elucidate whether other cellular processes are involved in amoebal pathogenicity and virulence. In comparison with virulent E. histolytica, the data indicated that the main reasons for the early clearance of nvEh from hamster liver are decreased intracellular H2 O2 detoxification rate and deficient heat shock protein expression, whereas for E. dispar, it is a relatively lower capacity for O2 reduction. Therefore, maintenance of an intracellular hypoxic environment combined with the induction of an adequate parasite response to oxidative stress are essential requirements for Entamoeba survival in the liver, and therefore for pathogenicity.
对细胞的黏附、细胞毒性和蛋白水解是溶组织内阿米巴毒力和致病性所需的功能。然而，在仓鼠实验性阿米巴肝脓肿中，这些体外功能与非致病性迪斯帕内阿米巴和无毒力溶组织内阿米巴（nvEh）的早期清除之间没有相关性。因此，可能还有其他功能参与了阿米巴的致病性和毒力。在本研究中，进行了一项全面的实验评估，包括用于分析阿米巴病理生理学、细胞生物学、生物化学和转录组学的创新技术，以阐明是否有其他细胞过程参与了阿米巴的致病性和毒力。与有毒力的溶组织内阿米巴相比，数据表明，nvEh在仓鼠肝脏中早期清除的主要原因是细胞内H2O2解毒率降低和热休克蛋白表达不足，而对于迪斯帕内阿米巴，原因是其O2还原能力相对较低。因此，维持细胞内低氧环境并诱导寄生虫对氧化应激产生适当反应是溶组织内阿米巴在肝脏中存活进而致病的必要条件。
