Estudio del mecanismo de acción de neurotoxinas botulínicas tipo A aisladas de cepas de C. botulinum autóctonas de Mendoza en modelos de cultivos celulares

Botulinum neurotoxin (BoNT) type A, produced by Clostridium botulinum (Cb), is the serotype prevalent in soil strains and cases of botulism in infants in Mendoza. Soil (Su) is the main reservoir of spores of the microorganism, and possibly the main source of infection for infants, producing infant b...

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Autores principales: Barrera, Patricia Andrea, Caballero, Patricia Alejandra, Chapana Albornoz, Agostina Lucía, Rivera, Daiana Beatriz, Sosa Paredes, Esteban David
Publicado: 2019
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Acceso en línea:https://bdigital.uncu.edu.ar/fichas.php?idobjeto=14459
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Sumario:Botulinum neurotoxin (BoNT) type A, produced by Clostridium botulinum (Cb), is the serotype prevalent in soil strains and cases of botulism in infants in Mendoza. Soil (Su) is the main reservoir of spores of the microorganism, and possibly the main source of infection for infants, producing infant botulism (IB). This physiopathological form has the highest incidence in Argentina. In previous studies we found that strains obtained from Su and feces of IB cases differ in the morphology of their colonies, in some biological properties of their BoNT, as well as in the proteolytic activity of BoNTs on SNARE proteins. We observed a correlation between increased toxic activity and cleavage of SNAP 25 and VAMP 2 by Su strains, with respect to strains of IB and prototype A Hall, this last characteristic without precedents. Both BoNT of Su and IB showed a molecular weight of 300 KDa, corresponding to the non-toxic non-haemagglutinating (M) complex, unlike what happens in other parts of the world where the NTBo producing strains of 900 and 600 KDa prevail respectively, with the hemagglutinating fraction (LL and L). Several authors suggest the entry of BoNT to the intestinal cells through the hemagglutinating fraction, which would lead to raise other internalization pathways for our toxins. This project proposes the study of the entry routes and the mechanism of action of the NTBos of native strains of Mendoza in different cell lines. The clarification of these mechanisms would allow to advance in the knowledge for further studies related to the blockade in the cellular uptake of the NTBo.