Genotype-Specific Small EVs Released by Giardia lamblia Act as Mediators of Phenotypic Adaptation Under Metronidazole-Induced Stress

Giardia lamblia, a eukaryotic intestinal parasite, produces small extracellular vesicles (sEVs) as a conserved evolutionary mechanism. This study investigates the functional role of sEVs in modulating drug response traits among G. lamblia parasites. Here, we showed that sEVs derived from metronidazole (MTZ)–resistant clones modify the expression of enzymes involved in MTZ metabolism and the production of reactive oxygen species (ROS) in recipient wild type parasites. The transfer efficiency and phenotypic impact vary depending on the genetic background of the isolates, highlighting a genotype-specific mechanism. Our findings reveal that sEVs act as mediators of phenotypic adaptation in G. lamblia, enhancing parasite survival under drug-induced stress. This study highlights the significance of sEVs in drug-sensitive dynamics and lays the groundwork for investigating therapeutic interventions that target EV-mediated sensitivity in giardiasis.