Anti-Pathogenic Properties of the Combination of a T3SS Inhibitory Halogenated Pyrrolidone with C-30 Furanone
Nelly Araceli Aburto-Rodríguez,
Naybi Muñoz-Cázares,
Víctor Alberto Castro-Torres,
Bertha González-Pedrajo,
Miguel Díaz-Guerrero,
Rodolfo García-Contreras,
Héctor Quezada,
Israel Castillo-Juárez,
Mariano Martínez-Vázquez
Affiliations
Nelly Araceli Aburto-Rodríguez
Departamento de Productos Naturales, Instituto de Química, Universidad Nacional Autónoma de México, Circuito Exterior, Ciudad Universitaria, Coyoacán, Ciudad de Mexico 04510, Mexico
Naybi Muñoz-Cázares
Laboratorio de Fitoquímica, Posgrado de Botánica, Colegio de Postgraduados, Texcoco 56230, Mexico
Víctor Alberto Castro-Torres
Departamento de Productos Naturales, Instituto de Química, Universidad Nacional Autónoma de México, Circuito Exterior, Ciudad Universitaria, Coyoacán, Ciudad de Mexico 04510, Mexico
Bertha González-Pedrajo
Departamento de Genética Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Ciudad de Mexico 04510, Mexico
Miguel Díaz-Guerrero
Departamento de Genética Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Ciudad de Mexico 04510, Mexico
Rodolfo García-Contreras
Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad Universitaria, Coyoacán, Ciudad de Mexico 04510, Mexico
Héctor Quezada
Laboratorio de Investigación en Inmunología y Proteómica, Hospital Infantil de México Federico Gómez, Ciudad de Mexico 06720, Mexico
Israel Castillo-Juárez
Laboratorio de Fitoquímica, Posgrado de Botánica, Colegio de Postgraduados, Texcoco 56230, Mexico
Mariano Martínez-Vázquez
Departamento de Productos Naturales, Instituto de Química, Universidad Nacional Autónoma de México, Circuito Exterior, Ciudad Universitaria, Coyoacán, Ciudad de Mexico 04510, Mexico
Antimicrobial resistance is one of the current public health challenges to be solved. The World Health Organization (WHO) has urgently called for the development of strategies to expand the increasingly limited antimicrobial arsenal. The development of anti-virulence therapies is a viable option to counteract bacterial infections with the possibility of reducing the generation of resistance. Here we report on the chemical structures of pyrrolidones DEXT 1–4 (previously identified as furan derivatives) and their anti-virulence activity on Pseudomonas aeruginosa strains. DEXT 1–4 were shown to inhibit biofilm formation, swarming motility, and secretion of ExoU and ExoT effector proteins. Also, the anti-pathogenic property of DEXT-3 alone or in combination with furanone C-30 (quorum sensing inhibitor) or MBX-1641 (type III secretion system inhibitor) was analyzed in a model of necrosis induced by P. aeruginosa PA14. All treatments reduced necrosis; however, only the combination of C-30 50 µM with DEXT-3 100 µM showed significant inhibition of bacterial growth in the inoculation area and systemic dispersion. In conclusion, pyrrolidones DEXT 1–4 are chemical structures capable of reducing the pathogenicity of P. aeruginosa and with the potential for the development of anti-virulence combination therapies.
