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Title: Sex steroids induce membrane stress responses and virulence properties in Pseudomonas aeruginosa
Authors: Vidaillac, Celine
Yong, Valerie Fei Lee
Aschtgen, Marie-Stephanie
Qu, Jing
Yang, Shuowei
Xu, Guangfu
Seng, Zi Jing
Brown, Alexandra C.
Ali, Md Khadem
Jaggi, Tavleen K.
Sankaran, Jagadish
Foo, Yong Hwee
Righetti, Francesco
Nedumaran, Anu Maashaa
Mac Aogáin, Micheál
Roizman, Dan
Richard, Jean-Alexandre
Rogers, Thomas R.
Toyofuku, Masanori
Luo, Dahai
Loh, Edmund
Wohland, Thorsten
Czarny, Bertrand
Horvat, Jay C.
Hansbro, Philip M.
Yang, Liang
Li, Liang
Normark, Staffan
Henriques-Normark, Birgitta
Chotirmall, Sanjay H.
Keywords: Science::Medicine
Issue Date: 2020
Source: Vidaillac, 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.01774-20
Project: MOH-000141
Journal: mBio
Abstract: Estrogen, 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.
ISSN: 2161-2129
DOI: 10.1128/mBio.01774-20
Rights: © 2020 Vidaillac et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

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