Toledo Max Jean de Ornelas, Bahia Maria Terezinha, Carneiro Cláudia M, Martins-Filho Olindo Assis, Tibayrenc Michel, Barnabé Christian, Tafuri Washington Luis, de Lana Marta
Departamento Análises Clínicas, Centro de Ciências da Saúde, Universidade Estadual de Maringá, Maringá, Brazil.
Antimicrob Agents Chemother. 2003 Jan;47(1):223-30. doi: 10.1128/AAC.47.1.223-230.2003.
The benznidazole (BZ) and itraconazole (ITC) susceptibilities of a standard set of Trypanosoma cruzi natural stocks were evaluated during the acute phase and the chronic phase of experimental chagasic infection in BALB/c mice. Twenty laboratory-cloned stocks representative of the total phylogenetic diversity of T. cruzi, including genotypes 20 and 19 (T. cruzi I) and genotypes 39 and 32 (T. cruzi II), were analyzed. Our results demonstrate important differences among stocks that could be pointed out as markers of biological behavior. Members of the T. cruzi I group were highly resistant to both BZ and ITC, whereas members of the T. cruzi II group were partially resistant to both drugs, despite their susceptibilities to ITC during the chronic phase of infection. The resistance to BZ observed for T. cruzi I was mainly triggered by genotype 20 isolates, whereas resistance to ITC was due to both genotype 20 and 19 isolates. Two polar patterns of response to BZ observed for genotype 39 isolates had a major impact on the partial resistance pattern observed for members of the T. cruzi II group. Genotype 32 isolates showed a typical profile of susceptibility. The correlation between the response to treatment and phylogenetic classification of T. cruzi stocks was clearer for ITC than for BZ. In conclusion, the data presented show a correlation between phylogenetic divergence among T. cruzi stocks and their susceptibilities to chemotherapeutic agents in vivo. Our results warn of the necessity to take into account the lesser genetic subdivisions of T. cruzi stocks since the upper subdivisions (T. cruzi I and II) show a great deal of heterogeneity for in vivo drug susceptibility.
在BALB/c小鼠实验性恰加斯病感染的急性期和慢性期，评估了一组克氏锥虫天然株系对苯硝唑（BZ）和伊曲康唑（ITC）的敏感性。分析了20个实验室克隆株系，它们代表了克氏锥虫的全部系统发育多样性，包括基因型20和19（克氏锥虫I）以及基因型39和32（克氏锥虫II）。我们的结果表明，各株系之间存在重要差异，这些差异可被视为生物学行为的标志物。克氏锥虫I组的成员对BZ和ITC均具有高度抗性，而克氏锥虫II组的成员对这两种药物均部分耐药，尽管它们在感染的慢性期对ITC敏感。克氏锥虫I对BZ的抗性主要由基因型20分离株引发，而对ITC的抗性则归因于基因型20和19分离株。在基因型39分离株中观察到的对BZ的两种极端反应模式，对克氏锥虫II组成员观察到的部分耐药模式产生了重大影响。基因型32分离株表现出典型的敏感特征。克氏锥虫株系对治疗的反应与系统发育分类之间的相关性，ITC比BZ更明显。总之，所呈现的数据表明克氏锥虫株系之间的系统发育差异与其在体内对化疗药物的敏感性之间存在相关性。我们的结果提醒人们，由于较高层次的分类（克氏锥虫I和II）在体内药物敏感性方面表现出很大的异质性，因此有必要考虑克氏锥虫株系较小的遗传亚分类。
