Unit of Molecular Parasitology, Department of Parasitology, Institute of Tropical Medicine, Antwerp, Belgium.
PLoS One. 2010 Aug 17;5(8):e12211. doi: 10.1371/journal.pone.0012211.
Leishmania donovani is an intracellular protozoan parasite that causes a lethal systemic disease, visceral leishmaniasis (VL), and is transmitted between mammalian hosts by phlebotomine sandflies. Leishmania expertly survives in these 'hostile' environments with a unique redox system protecting against oxidative damage, and host manipulation skills suppressing oxidative outbursts of the mammalian host. Treating patients imposes an additional stress on the parasite and sodium stibogluconate (SSG) was used for over 70 years in the Indian subcontinent.
METHODOLOGY/PRINCIPAL FINDINGS: We evaluated whether the survival capacity of clinical L. donovani isolates varies significantly at different stages of their life cycle by comparing proliferation, oxidative stress tolerance and infection capacity of 3 Nepalese L. donovani strains in several in vitro and in vivo models. In general, the two strains that were resistant to SSG, a stress encountered in patients, attained stationary phase at a higher parasite density, contained a higher amount of metacyclic parasites and had a greater capacity to cause in vivo infection in mice compared to the SSG-sensitive strain.
CONCLUSIONS/SIGNIFICANCE: The 2 SSG-resistant strains had superior survival skills as promastigotes and as amastigotes compared to the SSG-sensitive strain. These results could indicate that Leishmania parasites adapting successfully to antimonial drug pressure acquire an overall increased fitness, which stands in contrast to what is found for other organisms, where drug resistance is usually linked to a fitness cost. Further validation experiments are under way to verify this hypothesis.
杜氏利什曼原虫是一种细胞内原生动物寄生虫，可引起致命的全身性疾病——内脏利什曼病（VL），并通过白蛉沙蝇在哺乳动物宿主之间传播。利什曼原虫通过独特的氧化还原系统在这些“恶劣”环境中生存，该系统可防止氧化损伤，同时还具有宿主操纵技能，可抑制哺乳动物宿主的氧化爆发。治疗患者会给寄生虫带来额外的压力，而葡甲胺锑酸钠（SSG）在印度次大陆已使用了 70 多年。
方法/主要发现：我们通过比较 3 株来自尼泊尔的利什曼原虫分离株在几个体外和体内模型中的增殖、氧化应激耐受和感染能力，评估了其生命周期不同阶段的临床利什曼原虫分离株的生存能力是否存在显著差异。一般来说，对 SSG（患者中遇到的压力）具有抗性的两种菌株在寄生虫密度较高时达到静止期，含有更多的循环期寄生虫，并且与 SSG 敏感株相比，在体内感染小鼠的能力更强。
结论/意义：与 SSG 敏感株相比，这 2 株对 SSG 具有抗性的菌株作为前鞭毛体和无鞭毛体具有更好的生存能力。这些结果表明，成功适应锑剂压力的利什曼原虫寄生虫获得了整体更高的适应性，这与其他生物体的情况形成了鲜明对比，在其他生物体中，耐药性通常与适应性成本相关。正在进行进一步的验证实验来验证这一假设。
