Resistance to allopurinol in zoonotic canine leishmaniasis has been recently shown to be associated with disease relapse in naturally-infected dogs. However, information regarding the formation of resistance and its dynamics is lacking. This study describes the successful in-vitro induction of allopurinol resistance in Leishmania infantum cultured under increasing drug pressure. Allopurinol susceptibility and growth rate of induced parasites were monitored over 23 weeks and parasite clones were tested at selected time points and compared to their parental lines, both as promastigotes and as amastigotes. Allopurinol resistance was formed in strains from two parasite stocks producing a 20-fold rise in IC₅₀ along three distinct growth phases. In addition, characteristic differential clustering of single nucleotide polymorphisms (SNP) was found in drug sensitive and resistant parasite clones. Results confirm that genetic polymorphism, as well as clonal heterogeneity, contribute to in-vitro resistance to allopurinol, which is likely to occur in natural infection.

近来，在人畜共患的犬利什曼病中对别嘌呤醇的抗药性已被证明与自然感染犬的疾病复发有关。但是，缺乏有关阻力形成及其动力学的信息。这项研究描述了在增加药物压力下培养的婴儿利什曼原虫中成功地体外诱导别嘌醇抗性。在23周内监测别嘌呤醇的敏感性和诱导的寄生虫的生长速率，并在选定的时间点测试寄生虫的克隆，并与它们的亲本系比较，将其作为前鞭毛体和变形虫。在两种寄生虫菌种的菌株中形成了别嘌呤醇抗性，使IC ₅₀升高了20倍沿着三个不同的成长阶段。此外，在药物敏感性和耐药性寄生虫克隆中发现了单核苷酸多态性（SNP）的特征性差异簇。结果证实，遗传多态性以及克隆异质性有助于体外对别嘌呤醇的抗药性，这很可能发生在自然感染中。