title: Ambroxol interferes with Pseudomonas aeruginosa quorum sensing.
abstract: The mucolytic agent ambroxol has been reported to interfere with the formation of Pseudomonas aeruginosa-derived biofilms in addition to reducing alginate production by undefined mechanisms. Since quorum sensing is a key regulator of virulence and biofilm formation, we examined the effects of ambroxol on P. aeruginosa PAO1 wild-type bacterial clearance rates, adhesion profiles and biofilm formation compared with the quorum sensing-deficient, double-mutant strains DeltalasR DeltarhlR and DeltalasI DeltarhlI. Data presented in this report demonstrated that ambroxol treatment reduced survival rates of the double-mutant strains compared with the wild-type strain in a dose-dependent manner even though the double-mutants had increased adhesion in the presence of ambroxol compared with the wild-type strain. The PAO1 wild-type strain produced a significantly thicker biofilm (21.64+/-0.57 microm) compared with the biofilms produced by the DeltalasR DeltarhlR (7.36+/-0.2 microm) and DeltalasI DeltarhlI (6.62+/-0.31 microm) isolates. Ambroxol treatment reduced biofilm thickness, increased areal porosity, and decreased the average diffusion distance and textual entropy of wild-type and double-mutant strains. However, compared with the double-mutant strains, the changes observed for the wild-type strain were more clearly defined. Finally, ambroxol exhibited significant antagonistic quorum-sensing properties, suggesting that it could be adapted for use clinically in the treatment of cystic fibrosis and to reduce biofilm formation and in the colonisation of indwelling devices.
authors.affiliation: Department of Neonatology, Children's Hospital, Chongqing Medical University, Chongqing 400014, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Lu
authors.forename: Jialin
authors.initials: J
authors.lastname: Yu
authors.forename: Xiqiang
authors.initials: X
authors.lastname: Yang
authors.forename: Jiarong
authors.initials: J
authors.lastname: Wang
authors.forename: Lijia
authors.initials: L
authors.lastname: Wang
authors.forename: Yayin
authors.initials: Y
authors.lastname: Lin
authors.forename: Lihua
authors.initials: L
authors.lastname: Lin
mesh_terms: D000551:Ambroxol / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001422:Bacterial Adhesion; D006801:Humans; D050296:Microbial Viability / Q000187:drug effects; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000254:growth & development / Q000472:pathogenicity; D053038:Quorum Sensing / Q000187:drug effects*
chemical_list: D000900:Anti-Bacterial Agents; D000551:Ambroxol