Tetradecanoic Acids With Anti-Virulence Properties Increase the Pathogenicity of Pseudomonas aeruginosa in a Murine Cutaneous Infection Model

Frontiers in Cellular and Infection Microbiology

Bertha González-Pedrajo¹  Miguel Díaz-Guerrero¹  Rodolfo García-Contreras²  José Alberto Rivera-Chávez³  Mariano Martínez-Vázquez³  Ramón Marcos Soto-Hernández⁴  Humberto Cortes-López⁴  Israel Castillo-Juárez⁴  Martha María Juárez-Rodríguez⁴ 

[1] Departamento de Genética Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Ciudad de México, Mexico;Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad de México, Mexico;Departamento de Productos Naturales, Instituto de Química, Universidad Nacional Autónoma de México, Ciudad de México, Mexico;Laboratorio de Fitoquímica, Posgrado de Botánica, Colegio de Postgraduados, Texcoco, Mexico;

关键词: anti-virulence activity;    saturated fatty acids;    myristic acid;    lauric acid;    Pseudomonas aeruginosa;    quorum sensing;    type III secretion system;    animal model;   

DOI  :  10.3389/fcimb.2020.597517

来源: Frontiers

【 摘 要 】

Blocking virulence is a promising alternative to counteract Pseudomonas aeruginosa infections. In this regard, the phenomenon of cell-cell communication by quorum sensing (QS) is an important anti-virulence target. In this field, fatty acids (FA) have gained notoriety for their role as autoinducers, as well as anti-virulence molecules in vitro, like some saturated FA (SAFA). In this study, we analyzed the anti-virulence activity of SAFA with 12 to18 carbon atoms and compared their effect with the putative autoinducer cis-2-decenoic acid (CDA). The effect of SAFA on six QS-regulated virulence factors and on the secretion of the exoenzyme ExoU was evaluated. In addition, a murine cutaneous infection model was used to determine their influence on the establishment and damage caused by P. aeruginosa PA14. Dodecanoic (lauric, C12:0) and tetradecanoic (myristic, C14:0) acids (SAFA C12-14) reduced the production of pyocyanin by 35–58% at 40 and 1,000 µM, while CDA inhibited it 62% at a 3.1 µM concentration. Moreover, the SAFA C12-14 reduced swarming by 90% without affecting biofilm formation. In contrast, CDA reduced the biofilm by 57% at 3 µM but did not affect swarming. Furthermore, lauric and myristic acids abolished ExoU secretion at 100 and 50 µM respectively, while CDA reduced it by ≈ 92% at 100 µM. Remarkably, the coadministration of myristic acid (200 and 1,000 µM) with P. aeruginosa PA14 induced greater damage and reduced survival of the animals up to 50%, whereas CDA to 500 µM reduced the damage without affecting the viability of the PA14 strain. Hence, our results show that SAFA C12-14 and CDA have a role in regulation of P. aeruginosa virulence, although their inhibition/activation molecular mechanisms are different in complex environments such as in vivo systems.

【 授权许可】

CC BY