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

• Published in: Frontiers in cellular and infection microbiology Vol. 10; p. 597517
• Main Authors: Juárez-Rodríguez, Martha María, Cortes-López, Humberto, García-Contreras, Rodolfo, González-Pedrajo, Bertha, Díaz-Guerrero, Miguel, Martínez-Vázquez, Mariano, Rivera-Chávez, José Alberto, Soto-Hernández, Ramón Marcos, Castillo-Juárez, Israel
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 27-01-2021
• Subjects: Animals; Anti-Bacterial Agents - pharmacology; anti-virulence activity; Biofilms; Cellular and Infection Microbiology; lauric acid; Mice; myristic acid; Myristic Acids - pharmacology; Pseudomonas aeruginosa; Pseudomonas Infections; Quorum Sensing; saturated fatty acids; Virulence; Virulence Factors - pharmacology; myristic acid; quorum sensing; type III secretion system; Pseudomonas aeruginosa; saturated fatty acids; lauric acid; animal model; anti-virulence activity
• ISSN: 2235-2988; 2235-2988
• DOI: 10.3389/fcimb.2020.597517

Blocking virulence is a promising alternative to counteract
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
, 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
-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
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
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
virulence, although their inhibition/activation molecular mechanisms are different in complex environments such as
systems.