C.elegans as a model to find new therapeutic targets to control plant parasitic nematodes

SANTILLAN ZABALA V.J; MUNARRIZ ELIANA; MODENUTTI CARLOS; KRONBERG M.F.; CASTRO OA

Montevideo

Simposio; Symposium Expanding C. elegans research: First Latin American Worm Meeting; 2017

Instituto Pasteur de Montevideo

C.elegans as a model to find new therapeutic targets to control plant parasitic nematodesVanessa J. Santillán(1), María F. Kronberg (2) , Carlos Modenutti (1)Eliana R. Munarriz(2) and Olga A. Castro(1,3),1-IQUIBICEN (CONICET-UBA), Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón 2, Ciudad Universitaria, C1428EGA Buenos Aires, Argentina.2-INBA (CONICET-UBA) Facultad de Agronomía, Universidad de Buenos Aires. Av. San Martín 4453 C1417DSE, CABA, Argentina; Cátedra de Bioquímica, Facultad de Agronomía, Universidad de Buenos Aires, Av. San Martín 4453 C1417DSE, CABA, Argentina.3-Departamento de Fisiología, Biología Molecular y Celular. Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pabellón 2, Ciudad Universitaria, C1428EGA Buenos Aires, Argentina. alecastro2901@gmail.comUnder unfavorable conditions, such as overcrowding or scarcity of food, C.elegans L1 larvae can arrest development at an alternate L3 stage called diapause triggering the formation of ?dauer? larvae. When conditions are favorable, ?dauer? larvae emerges from diapause, and develops into a reproductive adult. What are the molecular pathways that govern dauer formation? The analysis of abnormal dauer formation mutants that either enter dauer constitutively or are defective in dauer formation showed that they comprise an endocrine network converging on the nuclear receptor DAF-12. Signals sensed in favorable environments promote the synthesis of DAF-12 steroid ligands called dafachronic acids (DA) which bind to DAF-12 and promote a reproductive life cycle. Under unfavorable conditions, ADs synthesis is suppressed, and unliganded DAF-12 promote the formation of dauer larvae. Meloidogyne species, known as root-knot nematodes (RKN), are one of the most important plant-parasitic nematodes worldwide. Based on the discovery of putative orthologous of several daf genes in different RKN, we hypothesized that the DAs mediated endocrine system was also functional in Meloidogyne spp. To determine if its components could be used as new therapeutic targets to control RKN, we identified the Ce daf-12 orthologous gene in M.incognita and analyzed if the 24-hydroxy-4-cholen-3-one (DAF-4), a CeDAF-12 antagonist, were able to control Meloidogyne life cycle. We isolated Meloidogyne eggs from infected tomato plants and analyzed the effect of this compound on egg hatching and infective J2 viability. We found a 53 % reduction in egg hatching and a 55 % increase in J2 mortality in presence of 200 µM DAF-4. We also studied the effect of DAf-4 on Meloidogyne infection in tomato plants. We found a 72% reduction in the number of galls/plant and a 56 % reduction in the number of eggs/egg masses when J2 were treated with DAF-4 100 µM. Taking together, our results indicate the DAs endocrine network may be functional in RKN and that DAF-4 is able to modulate Meloidogyne life cycle and infection. These findings suggest that other components of this system might constitute new molecular targets for the design of biotechnological strategies for the biological control of this plant parasite.