title: The effects of parabens on the mechanosensitive channels of E. coli.
abstract: Parabens are alkyl esters of p-hydroxybenzoic acid used as preservatives in a wide range of food, pharmaceutical, and cosmetic products. Despite their common use for over 50 years, their mechanism of action is still unclear. In this study we examined the effects of ethyl and propyl paraben, on gating of the E. coli mechanosensitive channel of large conductance (MscL) reconstituted into azolectin liposomes. We found that propyl and ethyl paraben spontaneously activate MscL. Moreover, the addition of propyl paraben caused an increase in MscL activity and the lowering of p(1/2), the pressure at which the MscL was opened 50% of the time, the DeltaG(o), the free energy required to open the MscL, and the parameter alpha, which describes the channel sensitivity to pressure. In addition, in silico studies showed that propyl paraben binds to the channel gate of the MscL. The mechanosensitive channel of small conductance was also found to be spontaneously activated by parabens. In summary, our study indicates that one of the previously unidentified mechanisms of action of parabens as antimicrobial agents is via an interaction with the mechanosensitive channels to upset the osmotic gradients in bacteria.
authors.affiliation: School of Medicine and Pharmacology, QEII Medical Centre, The University of Western Australia, Crawley, WA 6009, Australia.
authors.forename: Thom
authors.initials: T
authors.lastname: Nguyen
authors.forename: Brian
authors.initials: B
authors.lastname: Clare
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.forename: Boris
authors.initials: B
authors.lastname: Martinac
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry; D001703:Biophysics / Q000379:methods; D003593:Cytoplasm / Q000378:metabolism; D004492:Edetic Acid / Q000494:pharmacology; D004594:Electrophysiology; D004926:Escherichia coli / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D029968:Escherichia coli Proteins / Q000378:metabolism; D006531:HEPES / Q000494:pharmacology; D015640:Ion Channel Gating; D007473:Ion Channels / Q000737:chemistry / Q000378:metabolism; D008081:Liposomes / Q000737:chemistry; D008958:Models, Molecular; D009995:Osmosis; D010226:Parabens / Q000494:pharmacology*; D011310:Preservatives, Pharmaceutical / Q000494:pharmacology; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D013104:Spheroplasts / Q000737:chemistry / Q000378:metabolism; D013997:Time Factors
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D007473:Ion Channels; D008081:Liposomes; C086596:MscL protein, E coli; C469542:MscS protein, E coli; D010226:Parabens; D011310:Preservatives, Pharmaceutical; D004492:Edetic Acid; D006531:HEPES