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dc.contributor.authorVidaillac, Celineen_US
dc.contributor.authorYong, Valerie Fei Leeen_US
dc.contributor.authorAschtgen, Marie-Stephanieen_US
dc.contributor.authorQu, Jingen_US
dc.contributor.authorYang, Shuoweien_US
dc.contributor.authorXu, Guangfuen_US
dc.contributor.authorSeng, Zi Jingen_US
dc.contributor.authorBrown, Alexandra C.en_US
dc.contributor.authorAli, Md Khademen_US
dc.contributor.authorJaggi, Tavleen K.en_US
dc.contributor.authorSankaran, Jagadishen_US
dc.contributor.authorFoo, Yong Hweeen_US
dc.contributor.authorRighetti, Francescoen_US
dc.contributor.authorNedumaran, Anu Maashaaen_US
dc.contributor.authorMac Aogáin, Micheálen_US
dc.contributor.authorRoizman, Danen_US
dc.contributor.authorRichard, Jean-Alexandreen_US
dc.contributor.authorRogers, Thomas R.en_US
dc.contributor.authorToyofuku, Masanorien_US
dc.contributor.authorLuo, Dahaien_US
dc.contributor.authorLoh, Edmunden_US
dc.contributor.authorWohland, Thorstenen_US
dc.contributor.authorCzarny, Bertranden_US
dc.contributor.authorHorvat, Jay C.en_US
dc.contributor.authorHansbro, Philip M.en_US
dc.contributor.authorYang, Liangen_US
dc.contributor.authorLi, Liangen_US
dc.contributor.authorNormark, Staffanen_US
dc.contributor.authorHenriques-Normark, Birgittaen_US
dc.contributor.authorChotirmall, Sanjay H.en_US
dc.identifier.citationVidaillac, C., Yong, V. F. L., Aschtgen, M.-S., Qu, J., Yang, S., Xu, G., . . . Chotirmall, S. H. (2020). Sex steroids induce membrane stress responses and virulence properties in Pseudomonas aeruginosa. mBio, 11(5), e01774-20-. doi:10.1128/mBio.01774-20en_US
dc.description.abstractEstrogen, a major female sex steroid hormone, has been shown to promote the selection of mucoid Pseudomonas aeruginosa in the airways of patients with chronic respiratory diseases, including cystic fibrosis. This results in long-term persistence, poorer clinical outcomes, and limited therapeutic options. In this study, we demonstrate that at physiological concentrations, sex steroids, including testosterone and estriol, induce membrane stress responses in P. aeruginosa This is characterized by increased virulence and consequent inflammation and release of proinflammatory outer membrane vesicles promoting in vivo persistence of the bacteria. The steroid-induced P. aeruginosa response correlates with the molecular polarity of the hormones and membrane fluidic properties of the bacteria. This novel mechanism of interaction between sex steroids and P. aeruginosa explicates the reported increased disease severity observed in females with cystic fibrosis and provides evidence for the therapeutic potential of the modulation of sex steroids to achieve better clinical outcomes in patients with hormone-responsive strains. Importance: Molecular mechanisms by which sex steroids interact with P. aeruginosa to modulate its virulence have yet to be reported. Our work provides the first characterization of a steroid-induced membrane stress mechanism promoting P. aeruginosa virulence, which includes the release of proinflammatory outer membrane vesicles, resulting in inflammation, host tissue damage, and reduced bacterial clearance. We further demonstrate that at nanomolar (physiological) concentrations, male and female sex steroids promote virulence in clinical strains of P. aeruginosa based on their dynamic membrane fluidic properties. This work provides, for the first-time, mechanistic insight to better understand and predict the P. aeruginosa related response to sex steroids and explain the interindividual patient variability observed in respiratory diseases such as cystic fibrosis that are complicated by gender differences and chronic P. aeruginosa infection.en_US
dc.description.sponsorshipMinistry of Health (MOH)en_US
dc.description.sponsorshipNanyang Technological Universityen_US
dc.description.sponsorshipNational Medical Research Council (NMRC)en_US
dc.rights© 2020 Vidaillac et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.en_US
dc.titleSex steroids induce membrane stress responses and virulence properties in Pseudomonas aeruginosaen_US
dc.typeJournal Articleen
dc.contributor.schoolLee Kong Chian School of Medicine (LKCMedicine)en_US
dc.contributor.schoolSchool of Materials Science and Engineeringen_US
dc.contributor.researchSingapore Centre for Environmental Life Sciences and Engineering (SCELSE)en_US
dc.description.versionPublished versionen_US
dc.description.acknowledgementThis research was supported by the Singapore Ministry of Health’s National Medical Research Council under a clinician-scientist individual research grant (MOH-000141) awarded to S.H.C., the Lee Kong Chian School of Medicine (LKCMedicine), Nanyang Technological University, Singapore Start-Up grant to S.H.C., a grant from LKCMedicineto B.H.N. and S.N., the Swedish Research Council, the Knut and Alice Wallenberg Foundation and the Swedish Foundation for Strategic Research (SSF) to B.H.N. and S.N.,and a start-up grant from LKCMedicine to B.C. (M4082195).en_US
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