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

Luna Pizarro, G.; Laiolo, J.; Salas, N.; Patolsky, R. G.; Diaz Perez, L.; Cotello, C.; Feliziani, C.; Ropolo, A. S.; TOUZ, M. C.

doi:10.1101/2025.01.17.633589

bioRxiv · 10.1101/2025.01.17.633589

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

Luna Pizarro, G.·Laiolo, J.·Salas, N.·Patolsky, R. G.·Diaz Perez, L.·Cotello, C.·Feliziani, C.·Ropolo, A. S.·TOUZ, M. C.

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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 briefO_LISmall extracellular vesicles (sEVs) from Giardia lamblia mediate genotype-specific MTZ resistance transfer. C_LIO_LISmall extracellular vesicles from drug-resistant clones (RsEVs) alter enzyme expression and reactive oxygen species (ROS) production in recipient trophozoites. C_LIO_LIThe genetic background of G. lamblia isolates influences the effectiveness of resistance transfer. C_LIO_LIFindings provide insights into resistance mechanisms and potential targets for new giardiasis therapies. C_LI

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Luna Pizarro, G., Laiolo, J., Salas, N., Patolsky, R. G., Diaz Perez, L., Cotello, C., Feliziani, C., Ropolo, A. S., TOUZ, M. C.. 2025-01-20. Genotype-specific roles of small extracellular vesicles in modulating metronidazole resistance in Giardia lamblia. https://doi.org/10.1101/2025.01.17.633589

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