Abstract:
:Research on Giardia lamblia has accumulated large information about its molecular cell biology and infection biology. However, giardiasis is still one of the commonest parasitic diarrheal diseases affecting humans. Additionally, an alarming increase in cases refractory to conventional treatment has been reported in low prevalence settings. Consequently, efforts directed toward supporting the efficient use of alternative drugs, and the study of their molecular targets appears promising. Repurposing of proton pump inhibitors is effective in vitro against the parasite and the toxic activity is associated with the inhibition of the G. lamblia triosephosphate isomerase (GlTIM) via the formation of covalent adducts with cysteine residue at position 222. Herein, we evaluate the effectiveness of omeprazole in vitro and in situ on GlTIM mutants lacking the most superficial cysteines. We studied the influence on the glycolysis of Giardia trophozoites treated with omeprazole and characterized, for the first time, the morphological effect caused by this drug on the parasite. Our results support the effectiveness of omeprazole against GlTIM despite of the possibility to mutate the druggable amino acid targets as an adaptive response. Also, we further characterized the effect of omeprazole on trophozoites and discuss the possible mechanism involved in its antigiardial effect.
journal_name
Sci Repjournal_title
Scientific reportsauthors
López-Velázquez G,Fernández-Lainez C,de la Mora-de la Mora JI,Caudillo de la Portilla D,Reynoso-Robles R,González-Maciel A,Ridaura C,García-Torres I,Gutiérrez-Castrellón P,Olivos-García A,Flores-López LA,Enríquez-Flores Sdoi
10.1038/s41598-019-45529-wsubject
Has Abstractpub_date
2019-06-20 00:00:00pages
8922issue
1issn
2045-2322pii
10.1038/s41598-019-45529-wjournal_volume
9pub_type
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