Hemos trabajado en la identificación de moleculas de insectos susceptibles que medían la toxicidad de diferentes toxinas Cry producidas por Bt. Nuestros datos mostró que el modo de acción de estas toxinas es diferente explicando la efectividad de esta bacteria en el control de insectos y en evitar la evolución de resistencia. Sin embargo, todavía hay un vacio en el conocimineto del papel de the las diferentes proteínas del insecto en el modo de acción de diferentes toxinas Cry. La principal linea de investigación de nuestro laboratorio es en determinar las bases moleculares de la especificidad de las toxinas Cry. En particular el mapeo de los sitios de interacción en las toxinas y en los receptores para entender el mecanismo de especificifdad de estas toxinas. También en la identificación de receptores y el modo de acción de diferentes toxinas Cry con especificidad a diferentes ordenes de insecto como lepidopteros, coleopteros y dipteros.. Este conocimineto es fundamental para poder evolucionar la toxicidad y especificidad de estas proteínas.

Publicaciones

1. Guo, Z., Gong, L., Kang, Sh., Zhou, J., Sun, D., Qin, J., Guo, L., Zhu, L., Luo, L., Bai, Y., Bravo, A., Soberón, M., Zhang, Y. (2020) Comprehensive analysis of Cry1Ac protoxin activation mediated by midgut proteases in susceptible and resistant Plutella xylostella (L.). Pesticide Biochemistry and Physiology. 163: 23-30

2. Shabbir, M. Z., Zhang, T.-, Prabu, S., Wang, Y., Wang, Z., Bravo, A., Soberón, M., He, K (2020) Identification of Cry1Ah-binding proteins through pull down and gene expression analysis in Cry1Ah-resistant and susceptible strains of Ostrinia furnacalis. Pesticide Biochemistry and Physiology. 163: 200-208.

3. Wei, W., Pan, S., Ma, Y., Xiao, Y., Yang, Y., He, S., Bravo, A., Soberón, M., Liu, K. (2020) GATAe transcription factor is involved in Bacillus thuringiensis Cry1Ac toxin receptor gene expression inducing toxin susceptibility. Insect Biochemistry and Molecular Biology. 118: 103306.

4. Anaya, P., Onofre, J., Torres-Quintero, M. C., Sánchez, J., Gill, S. S., Bravo, A., Soberón, M (2020) Oligomerization is a key step for Bacillus thuringiensis Cyt1Aa insecticidal activity but not for toxicity against red blood cells. Insect Biochemistry and Molecular Biology. 119, 103317.

5. Gong, L., Kang, S., Zhou, J., Su, D., Guo, L., Qin, J., Zhu, L., Bai, Y., Ye, F., Mazarin, A., Wu, Q., Wang, S., Xu, B., Yang, Z., Bravo, A., Soberón, M., Guo, Z., We L., Zhang, Y (2020) Reduced expression of a novel midgut trypsin gene involved in protoxin activation correlates with Cry1Ac resistance in Plutella xylostella (L.). Toxins. 12: 76

6. do Nascimento, N. A., Torres-Quintero, M. C., López-Molina, S., Pacheco, S., Romão, T. P., Pereira-Neves, A., Soberón, M., Bravo, A., Neves Lobo Silva-Filha, M. H. (2020) Functional Bacillus thuringiensis Cyt1Aa is necessary to synergize Lysinibacillus sphaericus Binary toxin against Bin-resistant and refractory mosquito species. Applied and Environmental Microbiology. 86: (7)

7. Zheng, Z., Zhang, Y., Liu, Z., Xie, C., Bravo, A., Soberón, M., Mahillon, J., Sun, M., Peng, D. (2020) The CRISPR-Cas systems were selectively inactivated during evolution of Bacillus cereus group for adaptation to diverse environments ISMEJ. 14, 1479-1493.

8. Onofre., J., Pacheco, S., Torres-Quintero, M. C., Gill, S. S., Soberón. M., Bravo, A. (2020) The Cyt1Aa toxin from Bacillus thuringiensis inserts into target membranes via different mechanisms in insects, red blood cells, and lipid liposomes. Journal of Biological Chemistry. 295: 9606-9617

9. Zhang, J., Jin, M., Yang, Y., Liu, L., Yang, Y., Giomez, I., Bravo, A., Soberón, M., Xiao, Y., Liu, K. (2020) The cadherin protein is not Involved in susceptibility to Bacillus thuringiensis Cry1Ab and Cry1Fa Toxins in Spodoptera frugiperda. Toxins. 12: 375

10. Gómez, I., Ocelotl, J., Sánchez, J., Aguilar-Medel, S., Peña-Chora, G., Lina-García, L., Bravo, A., Soberón, M. (2020) Bacillus thuringiensis Cry1Ab domain III -22 mutants with enhanced toxicity to Spodoptera frugiperda (J. E. Smith). Applied and Environmental Microbiology. 86 (22)

11. Shu, C., Yan, G., Huang, S., Geng, Y., Soberón M., Bravo, A., Geng, L., Zhang, J. (2020) Characterization of two novel Cry8 toxins revealed differential specificity of protoxins or activated toxins against Chrysomiloidea superfamily. Toxins, 12: 642

12. Pacheco, S., Quiliche, J. P. J., Gomez, I., Sanchez, J., Soberón, M., Bravo, A. (2020) Rearengement of N-terminal alpha-helices of Bacillus thuringiensis Cry1Ab toxin essential for oligomer assembly and toxicity. Toxins, 12: E647.

13. Wang, Z., Wang, K., Bravo, A., Soberón, M., Cai, J., Shu, C., Zhang, J. (2020) Coexistance of Cry9 and Vip3 in an identical plasmid of Bacillus thuringiensis indicates their synergistic insecticidal toxicity. Journal of Agricultural and Food Chemistry, 68, 14081-14090.

14. Sena da Silva, I. H., Gomez, I., Pacheco, S., Sanchez, J., Zhang, J., Luque Castellane, T. C., Aparecida Desiderio, J., Soberón, M., Bravo, A., Polanczyk, R. A. (2021). Bacillus thuringiensis Cry1Ab domain III -16 is involved in binding to prohibitin which correlates with toxicity against Helicoverpa armigera (Lepidoptera: Noctuidae). Applied and Environmental Microbiology. 87 (2): e01930-20

15. Jin, M., Yang, Y., Shan, Y., Chakrabarty, S., Cheng, Y., Soberón, M., Bravo, A., Liu, K., Wu, K., Xiao, Y. (2021) Two ABC transporters are differentially involved in the toxicity of two Bacillus thuringiensis Cry1 toxins to the invasive crop-pest Spodoptera frugiperda (J. E. Smith) Pest Management Science. 77 (3), 1492-1501. DOI: 10-1002/ps/7160

16. Yang, Y., Huang, X., Yuan, W., Xiang, Y., Guo, X., Wei, W., Soberón, M., Bravo, A., Liu, K. (2021) Bacillus thuringiensis triggers autophagy activity that may enhance cell death. Pesticide Biochemistry and Physiology. 171: 104728

17. Wang, Z., Gan, C., Wang J., Bravo, A., Soberón, M., Yang, Q., Zhang, J. (2021) Nutrient conditions determine the localization of Bacillus thuringiensis Vip3Aa protein in the mother cell compartment. Microbial Biotechnology. 14: 551-560

18. López-Molina, S., do Nascimento, N. A., Neves Lobo Silva-Filha, M. A., Guerrero, A., Sánchez, J., Pacheco, S., Gill, S. S., Soberón, M., Baravo, A. (2021) In vivo nanoscale analysis of the dynamic synergistic interaction of Bacillus thuringiensis Cry11Aa and Cyt1Aa toxins in Aedes aegypti. Plos Pathogens. 176 (1), e1009199

19. Shi, J., Zhang, F., Chen, L., Bravo, A., Soberón, M., Sun, M. (2021) Sistemic mitochondrial disruption is a key event in the toxicity of bacterial pore-forming toxins to Caenorhabditis elegans. Environmemtal Microbiology. 23: 4896-4907

20. Liu, Y., Jin, M., Wang, L., Wang, H., Xia, Z., Yang, Y., Bravo, A., Soberón, M., Xiao., Y., Liu, K. 2021. SfABCC2 transporter extracellular loops 2 and 4 are responsible for the Cry1Fa insecticidal specificity against Spodoptera frugiperda. Insect Biochemistry and Molecular Biology. 135: 103608

21.Xiao,Y., Li,W., Yang,X., Xu,P., Jin,M., Yuan,H., Zheng,W., Soberon,M., Bravo,A., Wilson,K., Wu, K. (2021) Rapid spread of a densovirus in a major crop pest following wide-scale adoption of Bt-cotton in China. eLife 10, e66913.

22. Silva-Filha, M. H. N. L., Romao, T. P., Rezende, T. M. T., Carvalho, K. D. S., de Menezes, H. S. G., do Nascimento, N. A., Soberón, M., Bravo, A. (2021) Bacterial toxins active gainst mosquitoes: Mode of action and resistance. Toxins 13(8): 523.

23. Zhang, D., Jin, M., Yang, Y., Zhang, J., Yang, Y., Liu, K., Soberón, M., Bravo, A., Xiao,Y., Wu, K. (2021). Synergistic resistance of Helicoverpa armígera to Bt toxins linked to cadherin and ABC transporter mutations. Insect Biochemistry and Molecular Biology. 137: 103365.

24. Guo, Z., Kang, S., Wu, Q., Wang, S., Crickmore, N., Zhou, X., Bravo, A., Soberón, M., Zhang, Y. (2021) The regulation landscape of MAPK signaling cascade for thwarting Bacillus thuringiensis infection in an insect host. Plos Pathogens. 17: e1009917

25. Pacheco, S., Gómez, I., Chiñas, M., Sánchez, J., Soberón, M., Bravo, A. (2021) Whole Genome Sequencing Analysis of Bacillus thuringiensis GR007 Reveals Multiple Pesticidal Proteins. Frontiers in Microbiology. 12:758314.

26. Liao, C., Jin, M., Cheng, Y., Yang, Y., Soberón, M., Bravo,A., Liu, K., Xiao, Y. (2022) Bacillus thuringiensis Cry1Ac protoxin and activated toxin exert differential toxicity due to a synergistic interplay of cadherin with ABCC transporters in the cotton bollworm. Applied and Environmental Microbiology. 88:e02505-21

27. Sun, D., Zhu, L., Guo, L., Wang, S., Wu, Q., Crickmore, N., Zhou, X., Bravo, A., Soberón, M., Guo, Z., Zhang, Y. (2022) A versatile contribution of both aminopeptidases N and ABC transporters to Bt Cry1Ac toxicity in the diamondback moth. BMC Biology. 20 (1), 33

28. Guo, L., Cheng, Z., Qin, J., Sun, D., Wang, S., Wu, Q., Crickmore, N., Zhou, X., Bravo, A., Soberón, M., Guo, Z., Zhang, Y. (2022) MAPK-mediated transcription factor GATAd contributes to Cry1Ac resistance in diamondback moth by reducing PxmALP expression. Plos Genetics 18(2): e1010037

29. Bravo, A., Soberón, M. (2022) Mining versus in vitro evolution for the selection of novel insecticidal proteins. Microbial Biotechnology. 15: 2518-2520.

30. Guo, Z., Guo, L., Qin, J., Ye, F., Sun, D., Wu, Q., Wang, S., Crickmore, N., Zhou, X., Bravo, A., Soberón, M., and Zhang, Y. (2022) A single transcription factor facilitates an insect host combating Bacillus thuringiensis infection while maintaining fitness. Nature Communications 13:6024.

31. Pacheco, S., Gómez, I., Soberón, M., Bravo, A. (2023) A major conformational change of N-terminal helices of Bacillus thuringiensis Cry1Ab insecticidal protein is necessary for membrane insertion and toxicity. FEBS Journal. 290: 2692-2705

32. Pacheco, S., Gómez, I., Peláez-Aguilar, A. E., Verduzco-Rosas, L. A., García-Suárez, R., do Nascimento, N. A., Rivera-Nájera, L. Y., Cantón, P. E., Soberón, M., and Bravo, A. (2023) Structural changes upon membrane insertion of the insecticidal pore forming toxins produced by Bacillus thuringiensis. Frontiers in Insect Science. 3:1188891.

33. García-Gomez, B. I., Sánchez, T. A., Cano, S. N., Na do Nascimento, N. A., Bravo, A., and Soberón, M. (2023) Insect chaperones Hsp70 and Hsp90 cooperatively enhance toxicity of Bacillus thuringiensis Cry1A toxins and counteract insect resistance. Frontiers in Immunology. 14:1151943

34. Wang, K., Shu, Ch., Bravo, A., Soberón, M., Zhang, H., Neil Crickmore, N., Zhang, J. (2023) Development of an online genome sequence comparison resource for Bacillus cereus sensu lato strains using the efficient composition vector method. Toxins. 15, 393.

35. Chen, F., Pang, C., Zheng, Z., Zhou, W., Guo, Z., Du, H., Bravo, A., Soberón, M., Ming, S., Peng, D. (2023) Aminopeptidase MNP-1 triggers intestine protease production by activating daf-16 nuclear location to degrade pore-forming toxins in Caenorhabditis elegans. Plos pathogens. 19: e1011507

36. Bravo, A., Soberón, M. (2023) Can microbial based insecticides replace chemical pesticides in agricultural production? Micobial Biotechnology. https://doi.org/10.1111/1751-7915.14316

37. Wei, W., Wang, L., Pan, S., Wang, H., Xia, Z., Liu, L., Xiao, Y., Bravo, A., Soberón, M., Yang, Y., Liu, K. 2023. Helicoverpa armigera GATAe transcriptional factor regulates the expression of Bacillus thuringiensis Cry1Ac receptor gene ABCC2 by its interplay with additional transcription factors. Pesticide Biochemistry and Physiology. 194: 105516.

38. Velásquez-C, L-F., Canton, P. E., Sanchez-Flores, A., Soberón, M., Bravo, A., Cerón-S, J. (2023) Identification of Cry toxin receptor genes homologs in a de novo transcriptome of Premnotrypes vorax (Coleoptera: Curculionidae). PlosOne. 18: e0291546.

39. Wang, Z., Yang, Y., Li, S., Ma, W., Wang, K., Soberón, M., Yan, S., Shen, Y., Francis, F., Bravo, A., Zhang, J. (2024) JAK/STAT signaling regulated intestinal regeneration defends insect pests against pore-forming toxins produced by Bacillus thuringiensis. Plos pathogens. 24, e1011823.

40. He, X., Yang, Y, Soberón, M., Bravo, A., Zhang, L., Zhang, J., Wang, Z. (2024) Bacillus thuringiensis Cry9Aa insecticidal protein domain I helices a3 and a4 are two core regions involved in oligomerization and toxicity. Journal of Agricultural and Food Chemistry. 72: 1321-1329

41. de Oliveira, J. L., Gómez, I., Sánchez, J., Soberón, M., Polanczyk, R. A., Bravo, A (2024). Performance Insights into Spray-Dryer Microencapsulated Bacillus thuringiensis Cry Pesticidal Proteins with Gum Arabic and Maltodextrin for Effective Pest Control. Applied Microbiology and Biotechnology. 108:181

42. Timmis, K., Hallsworth, J. E., McGenity, T. J. Armstrong, R., Colom, M. F., Karahan, Z. C., Chavarría, M., Bernal, P., Boyd, E. S., Ramos, J. L., Kaltenpoth, M., Pruzzo, C., Clarke, G., Lopez-Garcia, P., Yakimov, M. M., Perlmutter, J., Greening, C., Eloe-Fadrosh, E., Verstraete, W., Nunes, O. C., Kotsyurbenko, O., Nikel, P. I., Scavone, P., Häggblom, M. M., Lavigne, R., Le Roux, F., James Timmis, J., Parro, V., Michán, C., García, J. L., Casadevall, A., Payne, S. M., Frey, J., Koren, O., Prosser, J. I., Lahti, L., Lal, R., Shailly Anand, S., Utkarsh Sood, U., Offre, P., Bryce, C. C., Mswaka, A. Y., Jores, J., Kaçar, B., Lars Mathias Blank, L. M., Maaßen, N., B. Pope, P. B., Banciu, H. L., Armitage, J., Lee, S. Y., Wang, F., Makhalanyane, T. P., Jack Gilbert, J., Wood, T. K., Vasiljevic, B., Soberon, M., Zulema Udaondo, Z., Rojo, F., Tamang, J. P., Tatiana Giraud, T., Ropars, J., Ezeji, T., Müller, V., Danbara, H., Beate Averhoff, B., Angela Sessitsch, A., Partida-Martínez, L. P., Huang, W., Molin, S., Junier, P., Ricardo Amils, R., Wu, X-L., Ron, E., Erten, H., Pereira de Martinis, E. C., Rapoport, A., Opik, M., Pokatong, W. D. R., Stairs, C., Mohammad Ali Amoozegar, M. A., Serna, J. G. (2024) A concept for international societally-relevant microbiology education and microbiology knowledge promulgation in society. Microbial Biotechnology. 17: e14456.

43. Huang, G., Cong, Z., Liu, Z., Chen, F., Bravo, A., Soberón, M., Zheng, J., Peng, D., Sun, M. (2024) Silencing Ditylenchus destructor cathepsin L-like cysteine protease has negative pleiotropic effect on nematode ontogenesis. Scientific Reports. 14: 10030

44. Pacheco, S., Gallegos, A. S., Pelaez-Aguilar, A. E., Sanchez, J., Gómez, I., Soberón, M., Bravo, A. (2024) CRISPR-Cas9 Knockout of Membrane-Bound Alkaline Phosphatase or Cadherin Does Not Confer Resistance to Cry Toxins in Aedes aegypti. Plos Neglected Tropical Diseases. 18: e0012256.

45. Wang, H., Li, A., Bian, H., Jin, L., Ma, S., Wang, H., Yang, Y., Bravo, A., Soberón, M., Liu, K. (2024) Transcriptional regulation of Cry2Ab toxin receptor ABCA2 gene in insexts involves GATAe and splicing of ant 5´ UTR intron. Pesticide Bioichemistry and Physiology. 206: 106211

46. Infante, O., Gómez, I., Pelaez-Aguilar, A. E., Verduzco-Rosas, L. A., Garcá-Suarez, R, García-Gómez, B. I., Wang, Z., Zhang, J., Guerrero, A., Bravo, A., Soberón, M. (2024). Insights into the structural changes that trigger receptor binding upon proteolytic activation of Bacillus thuringiensis Vip3Aa insecticidal protein. Plos Pathogens. 20: e1012765.

47. Sun, D., Xu, Q., Guo, L., Bai, Y., Shentu, X., Yu, X., Crickmore, N., Zhou, X., Bravo, A., Soberón, M., Zhang, Y.. Guo, Z. (2025) The role of GPI-anchored membrane-bound alkaline phosphatase in the mode of action of Bt Cry1A toxins in the diamondback moth. Fundamental Research. 5:674-682 

48. Wang, K., Xu, J., Lu, X., Yin, P., Chen, L., Zhao, Z., Bravo, A., Soberón, M., Zhen, J., Sun, M., Peng, D. (2025) Two novel trimethoprim resistance genes, dfrA50 and dfrA51, identified in phage-plasmids. Antimicrobial Agents and Chemoterapy. In the press

49. Tan, S., Shang, Z., Jia, H., Huang, J., Geng, L., Shu, C., Soberón, M., Bravo, A., Shi, W., Zhang, J., Hongshuang Wei,H. (2025) Enhancing Bacillus thuringiensis Cry8Ea1 toxicity: Insights into protease sensitivity for the evolutionary adaptation of Cry toxins to insect hosts. International Journal of Biological Macromolecules, 308, 142246.

50. Li, S., Wang, Z., Yang, Y., Niu, X., Fang, Y., Soberón, M., Bravo, A., Wu, G-X., Zhang, J. (2025) Sequestosome 1 in autophagy regulates a defense response of the striped stem borer to the Cry9Aa protein. Journal of Agricultural and Food Chemistry. 73:11030-11040

51. López-Molina, S., Guerrero, A., Pacheco, S., Wang, Z., Zhang, J., Sanchez, J., Zavala, G., Soberón, M., Bravo, A. (2025) Cry11Aa Toxin of Bacillus thuringiensis interactions with intracellular organelles in Insect gut Implicating Actin Depolymerization, Massive Endocytosis, and Vesicle Secretion. International Journal of Biological Macoromolecules. 314, 144350

Circuito de Posgrado, Ciudad Universitaria
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