Abstract
Vibrio cholerae causes cholera and is the leading cause of diarrhea in developing countries, highlighting the need for the development of new treatment strategies to combat this disease agent. While exploring the possibility of using zinc oxide (ZnO) nanoparticles (NPs) in cholera treatment, we previously found that ZnO NPs reduce fluid accumulation in mouse ileum induced by the cholera toxin (CT) protein. To uncover the mechanism of action of ZnO NPs on CT activity, here we used classical (O395) and El Tor (C6706) V. cholerae biotypes in growth and biochemical assays. We found that a ZnO NP concentration of 10 μg/ml did not affect the growth rates of these two strains, nor did we observe that ZnO NPs reduce the expression levels of CT mRNA and protein. It was observed that ZnO NPs form a complex with CT, appear to disrupt the CT secondary structure, and block its interaction with the GM1 ganglioside receptor in the outer leaflet of the plasma membrane in intestinal (HT-29) cells and thereby reduce CT uptake into the cells. In the range of 2.5-10 μg/ml, ZnO NPs exhibited no cytotoxicity on kidney (HEK293) and HT-29 cells. We conclude that ZnO NPs prevent the first step in the translocation of cholera toxin into intestinal epithelial cells without exerting measurable toxic effects on HEK293 and HT-29 cells.
Highlights
In 2015, the WHO reported 172,454 cases and 1340 deaths in 42 countries due to cholera [1]; the impact of this is enormous on society [2]
We explored the classical GM1 ganglioside-based ELISA for detecting the secreted cholera toxin (CT) level in the supernatant of the culture grown alone and in the presence of zinc oxide (ZnO) NP (0 –50 g/ml) under CT-induced conditions
Because ZnO NP exhibits no effect on CT production and secretion, we studied if ZnO NP binds to the GM1 receptor and inhibits its activity to attach with CT
Summary
Vibrio cholerae causes cholera and is the leading cause of diarrhea in developing countries, highlighting the need for the development of new treatment strategies to combat this disease agent. To uncover the mechanism of action of ZnO NPs on CT activity, here we used classical (O395) and El Tor (C6706) V. cholerae biotypes in growth and biochemical assays. We conclude that ZnO NPs prevent the first step in the translocation of cholera toxin into intestinal epithelial cells without exerting measurable toxic effects on HEK293 and HT-29 cells. V. cholerae may share this gene with other enteric pathogens and in the process may complicate the treatment for an array of infections [19]. These conditions necessitate the finding of a new therapeutic strategy for the proper management of the disease. The World Health Organization recommends oral zinc combined with ORS as an effective therapy to decrease the morbidity and mor-
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