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Anti-Pathogenic Properties of the Combination of a T3SS Inhibitory Halogenated Pyrrolidone with C-30 Furanone

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...

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Autores principales: Aburto-Rodríguez, Nelly Araceli, Muñoz-Cázares, Naybi, Castro-Torres, Víctor Alberto, González-Pedrajo, Bertha, Díaz-Guerrero, Miguel, García-Contreras, Rodolfo, Quezada, Héctor, Castillo-Juárez, Israel, Martínez-Vázquez, Mariano
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8707098/
https://www.ncbi.nlm.nih.gov/pubmed/34946717
http://dx.doi.org/10.3390/molecules26247635
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author Aburto-Rodríguez, Nelly Araceli
Muñoz-Cázares, Naybi
Castro-Torres, Víctor Alberto
González-Pedrajo, Bertha
Díaz-Guerrero, Miguel
García-Contreras, Rodolfo
Quezada, Héctor
Castillo-Juárez, Israel
Martínez-Vázquez, Mariano
author_facet Aburto-Rodríguez, Nelly Araceli
Muñoz-Cázares, Naybi
Castro-Torres, Víctor Alberto
González-Pedrajo, Bertha
Díaz-Guerrero, Miguel
García-Contreras, Rodolfo
Quezada, Héctor
Castillo-Juárez, Israel
Martínez-Vázquez, Mariano
author_sort Aburto-Rodríguez, Nelly Araceli
collection PubMed
description 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.
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spelling pubmed-87070982021-12-25 Anti-Pathogenic Properties of the Combination of a T3SS Inhibitory Halogenated Pyrrolidone with C-30 Furanone Aburto-Rodríguez, Nelly Araceli Muñoz-Cázares, Naybi Castro-Torres, Víctor Alberto González-Pedrajo, Bertha Díaz-Guerrero, Miguel García-Contreras, Rodolfo Quezada, Héctor Castillo-Juárez, Israel Martínez-Vázquez, Mariano Molecules Article 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. MDPI 2021-12-16 /pmc/articles/PMC8707098/ /pubmed/34946717 http://dx.doi.org/10.3390/molecules26247635 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Aburto-Rodríguez, Nelly Araceli
Muñoz-Cázares, Naybi
Castro-Torres, Víctor Alberto
González-Pedrajo, Bertha
Díaz-Guerrero, Miguel
García-Contreras, Rodolfo
Quezada, Héctor
Castillo-Juárez, Israel
Martínez-Vázquez, Mariano
Anti-Pathogenic Properties of the Combination of a T3SS Inhibitory Halogenated Pyrrolidone with C-30 Furanone
title Anti-Pathogenic Properties of the Combination of a T3SS Inhibitory Halogenated Pyrrolidone with C-30 Furanone
title_full Anti-Pathogenic Properties of the Combination of a T3SS Inhibitory Halogenated Pyrrolidone with C-30 Furanone
title_fullStr Anti-Pathogenic Properties of the Combination of a T3SS Inhibitory Halogenated Pyrrolidone with C-30 Furanone
title_full_unstemmed Anti-Pathogenic Properties of the Combination of a T3SS Inhibitory Halogenated Pyrrolidone with C-30 Furanone
title_short Anti-Pathogenic Properties of the Combination of a T3SS Inhibitory Halogenated Pyrrolidone with C-30 Furanone
title_sort anti-pathogenic properties of the combination of a t3ss inhibitory halogenated pyrrolidone with c-30 furanone
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8707098/
https://www.ncbi.nlm.nih.gov/pubmed/34946717
http://dx.doi.org/10.3390/molecules26247635
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