Vande Voorde J, Liekens S, Gago F, Balzarini J
a Rega Institute for Medical Research , KU Leuven , Leuven , Belgium.
Nucleosides Nucleotides Nucleic Acids. 2014;33(4-6):394-402. doi: 10.1080/15257770.2013.851394.
Mycoplasmas are opportunistic parasites and some species are suggested to preferentially colonize tumor tissue in cancer patients. We could demonstrate that the annotated thymidine phosphorylase (TP) gene in the genome of Mycoplasma hyorhinis encodes a pyrimidine nucleoside phosphorylase (PyNPHyor) that not only efficiently catalyzes thymidine but also uridine phosphorolysis. The kinetic characteristics of PyNPHyor-catalyzed nucleoside and nucleoside analogue (NA) phosphorolysis were determined. We demonstrated that the expression of such an enzyme in mycoplasma-infected cell cultures dramatically alters the activity of various anticancer/antiviral NAs such as 5-halogenated pyrimidine nucleosides, including 5-trifluorothymidine (TFT). Due to their close association with human cancers, the presence of mycoplasmas may markedly influence the therapeutic efficiency of nucleoside-based drugs.
支原体是机会性寄生虫，有研究表明某些支原体物种会优先定殖于癌症患者的肿瘤组织中。我们能够证明，猪鼻支原体基因组中注释的胸苷磷酸化酶（TP）基因编码一种嘧啶核苷磷酸化酶（PyNPHyor），它不仅能高效催化胸苷，还能催化尿苷的磷酸解反应。我们测定了PyNPHyor催化核苷和核苷类似物（NA）磷酸解反应的动力学特征。我们证明，在支原体感染的细胞培养物中这种酶的表达会显著改变各种抗癌/抗病毒核苷类似物的活性，如5-卤代嘧啶核苷，包括5-三氟胸苷（TFT）。由于支原体与人类癌症密切相关，其存在可能会显著影响核苷类药物的治疗效果。
