Department of Pathology and Microbiology, Faculty of Veterinary Medicine, Université de Montréal, 626 CIMIA Sicotte Street, Saint-Hyacinthe, QC J2S 2M2, Canada; The Research Group on Infectious Diseases in Production Animals (GREMIP), Faculty of Veterinary Medicine, University of Montreal, Saint-Hyacinthe, QC J2S 2M2, Canada.
IDIGH, The Research Institute of the McGill University Health Centre, 2155 Guy Street, Montreal, QC H3H 2L9, Canada.
Cell Rep. 2022 Jul 19;40(3):111121. doi: 10.1016/j.celrep.2022.111121.
Leishmania are eukaryotic parasites that have retained the ability to produce extracellular vesicles (EVs) through evolution. To date, it has been unclear if different DNA entities could be associated with Leishmania EVs and whether these could constitute a mechanism of horizontal gene transfer (HGT). Herein, we investigate the DNA content of EVs derived from drug-resistant parasites, as well as the EVs' potential to act as shuttles for DNA transfer. Next-generation sequencing and PCR assays confirm the enrichment of amplicons carrying drug-resistance genes associated with EVs. Transfer assays of drug-resistant EVs highlight a significant impact on the phenotype of recipient parasites induced by the expression of the transferred DNA. Recipient parasites display an enhanced growth and better control of oxidative stress. We provide evidence that eukaryotic EVs function as efficient mediators in HGT, thereby facilitating the transmission of drug-resistance genes and increasing the fitness of cells when encountering stressful environments.
利什曼原虫是真核寄生虫，通过进化保留了产生细胞外囊泡（EVs）的能力。迄今为止，尚不清楚不同的 DNA 实体是否可以与利什曼原虫 EVs 相关联，以及这些是否可以构成水平基因转移（HGT）的机制。在此，我们研究了来自耐药寄生虫的 EVs 的 DNA 含量，以及 EVs 作为 DNA 转移载体的潜力。下一代测序和 PCR 检测证实了与 EVs 相关的耐药基因的扩增子的富集。耐药 EVs 的转移实验突出表明，通过转移 DNA 的表达，对受纳寄生虫表型产生显著影响。受纳寄生虫表现出增强的生长和更好的氧化应激控制。我们提供的证据表明，真核 EVs 作为 HGT 的有效介质，从而促进耐药基因的传播，并在遇到应激环境时增加细胞的适应性。
