title: Aspirin is an efficient inhibitor of quorum sensing, virulence and toxins in Pseudomonas aeruginosa.
abstract: Quorum sensing (QS) plays a vital role in regulation of virulence factors and toxins in Pseudomonas aeruginosa, which can cause serious human infections. Therefore, the QS system in P. aeruginosa may be an important target for pharmacological intervention. Activity of aspirin on the QS system was assessed using a reporter strain assay and confirmed using RT-PCR to test expression of virulence factors and toxins. In addition, molecular modeling techniques including docking, flexible alignment and surface mapping were also applied to further understand aspirin's potential QS inhibition activity. Aspirin (6 mg/ml) showed significant reduction (p < 0.01) of quorum sensing signals in P. aeruginosa, including expression of elastase, total proteases, and pyocyanin (p < 0.01) without affecting bacterial viability. Aspirin also significantly reduced organism motility and biofilm production (p < 0.01) and decreased expression of lasI, lasR, rhlI, rhlR, pqsA and pqsR genes by 38, 72, 69, 72, 74 and 43% respectively. Moreover, the expression of Pseudomonas toxins exoS and exoY was reduced by 47 and 55% respectively. The molecular modeling analysis suggests the QS inhibitory action of aspirin occurs through interaction of aspirin's aryl group and Tyr-88 of the LasR receptor, by strong π-π stacking interactions, which associated with a conformational change of the receptor-aspirin complex. The inhibitory effect of aspirin on virulence factors was specific to P. aeruginosa as aspirin at sub-MIC did not affect the biofilm or motility of Escherichia coli. To summarize, the collective data demonstrate that low concentrations of aspirin inhibit quorum sensing of P. aeruginosa.
authors.affiliation: Department of Microbiology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt. Electronic address: dr_msm4e2013@hotmail.com.
authors.forename: Somaia A
authors.initials: SA
authors.lastname: El-Mowafy
authors.affiliation: Department of Microbiology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt. Electronic address: kelgalil@hotmail.com.
authors.forename: Khaled H
authors.initials: KH
authors.lastname: Abd El Galil
authors.affiliation: Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura 35516, Egypt. Electronic address: shahenda76@yahoo.com.
authors.forename: Shahenda M
authors.initials: SM
authors.lastname: El-Messery
authors.affiliation: Department of Microbiology, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt. Electronic address: mona_ibrahem@mans.edu.eg.
authors.forename: Mona I
authors.initials: MI
authors.lastname: Shaaban
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000096:biosynthesis; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors*; D004926:Escherichia coli / Q000187:drug effects; D020869:Gene Expression Profiling; D006801:Humans; D008124:Locomotion / Q000187:drug effects; D050296:Microbial Viability / Q000187:drug effects; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000502:physiology*; D053038:Quorum Sensing / Q000187:drug effects*; D014774:Virulence / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D001241:Aspirin
keywords: Aspirin; Pseudomonas aeruginosa; Quorum sensing; Toxins; Virulence