Genotype-specific roles of small extracellular vesicles in modulating metronidazole resistance in Giardia lamblia

Authors:
Preprint
Publisher website
Google Scholar
Abstract
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 transferring drug-resistance traits among parasites. sEVs derived from metronidazole (MTZ)-resistant clones are shown to modify the expression of enzymes involved in MTZ metabolism and the production of reactive oxygen species (ROS) in recipient wild-type parasites. These changes significantly alter the drug sensitivity of recipient 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 underscores the importance of sEVs in drug-resistance dynamics and provides a basis for exploring therapeutic interventions targeting EV-mediated resistance in giardiasis. Highlights In brief: Small extracellular vesicles (sEVs) from Giardia lamblia mediate genotype-specific MTZ resistance transfer. Small extracellular vesicles from drug-resistant clones (RsEVs) alter enzyme expression and reactive oxygen species (ROS) production in recipient trophozoites. The genetic background of G. lamblia isolates influences the effectiveness of resistance transfer. Findings provide insights into resistance mechanisms and potential targets for new giardiasis therapies.

This publication has 75 references indexed in Scilit: