Tetradecanoic Acids With Anti-Virulence Properties Increase the Pathogenicity of Pseudomonas aeruginosa in a Murine Cutaneous Infection Model.
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.
['Juárez-Rodríguez|Martha María|MM|', 'Cortes-López|Humberto|H|', 'García-Contreras|Rodolfo|R|', 'González-Pedrajo|Bertha|B|', 'Díaz-Guerrero|Miguel|M|', 'Martínez-Vázquez|Mariano|M|', 'Rivera-Chávez|José Alberto|JA|', 'Soto-Hernández|Ramón Marcos|RM|', 'Castillo-Juárez|Israel|I|']
D000818:Animals D000900:Anti-Bacterial Agents D018441:Biofilms D051379:Mice D009227:Myristic Acids D011552:Pseudomonas Infections D011550:Pseudomonas aeruginosa D053038:Quorum Sensing D014774:Virulence D037521:Virulence Factors
Pseudomonas aeruginosa quorum sensing anti-virulence activity myristic acid animal model lauric acid saturated fatty acids type III secretion system