Journal Article

Palmitoleic acid inhibits Pseudomonas aeruginosa quorum sensing activation and protects lungs from infectious injury

Ren, Jie, Xie, Guogang, Gao, Jianwei, Xue, Yishu, Zhu, Hui, Han, Lei, Ding, Fengming, Shao, Ping, Fu, Qiang, Zhang, Min

2024

Overview

Background Unsaturated fatty acids targeting quorum sensing (QS) system have shown potential application in reducing bacterial virulence. We aim to investigate the effect of palmitoleic acid (PMA) on P. aeruginosa QS activation, and its impact on infection-induced lung injury. Methods The influence of PMA on QS signaling molecule (3OC12-HSL and C4-HSL) concentrations, pyocyanin production, and QS gene transcription levels were examined in wildtype PAO1 culture. The roles of PMA in reducing infection-induced injury were assessed in human bronchial epithelial BEAS-2B cells and mouse lung infection models, respectively. PMA levels and QS signaling molecule concentrations were tested in the bronchoalveolar lavage fluid (BALF) of bronchiectasis patients with first-time detection of P. aeruginosa infection. Results PMA administration dose-dependently suppressed the expression of QS signaling molecules, pyocyanin, and QS genes during the logarithmic stage of bacterial growth. In BEAS-2B cells, PMA-treated PAO1 filtrates significantly reduced cell apoptosis and expression of IL-8 and IL-6. In mouse lung infection models, prophylactically oral administration of PMA significantly downregulated the expression of P. aeruginosa QS signals and QS genes ( lasR , rhlR , rhlI , lasB , rhlA , phzA1 , phnA ) in lungs, and relieved neutrophilic airway inflammation. Finally, PMA levels were negatively correlated with the concentrations of both 3OC12-HSL and C4-HSL in BALF of bronchiectasis patients, and positively correlated with their forced vital capacity (FVC) and forced expiratory volume in the first second (FEV 1.0 ) . Conclusion Our findings show that PMA inhibits P. aeruginosa QS activation and protects lungs from injury caused by bacterial virulence. Hence, PMA may serve as a potential anti-QS agent against P. aeruginosa infection and would help to alleviate lung injury in bronchiectasis patients.

• Publisher: BioMed Central,BioMed Central Ltd,Nature Publishing Group,BMC
• Subject: Analysis / Animal models / Animals / Apoptosis / Biofilms / Bronchiectasis / Bronchopulmonary infection / Bronchus / Carbon / Care and treatment / Cell culture / Cell cycle / Cellulose acetate / Composition / Control / Fatty acids / Fatty Acids, Monounsaturated - pharmacology / Female / Genes / Genetic aspects / Health aspects / Humans / Identification and classification / Infection control / Infection-induced injury / Infections / Injuries / Lavage / Leukocytes (neutrophilic) / Lung - drug effects / Lung - metabolism / Lung - microbiology / Lung diseases / Lung infection / Lungs / Male / Medicine / Medicine & Public Health / Methods / Mice / Mice, Inbred BALB C / Monounsaturated fatty acids / Multidrug resistant organisms / Oral administration / Palmitoleic acid / Pathogens / Phorbol esters / Pneumology/Respiratory System / Pseudomonas aeruginosa / Pseudomonas aeruginosa - drug effects / Pseudomonas aeruginosa - physiology / Pseudomonas Infections - drug therapy / Pseudomonas Infections - metabolism / Pseudomonas Infections - microbiology / Pseudomonas Infections - prevention & control / Pyocyanin / Quorum sensing / Quorum Sensing - drug effects / Respiratory tract diseases / RhlR protein / Risk factors / Software / Spirometry / Virulence / Virulence (Microbiology)