Sex Steroids Induce Membrane Stress Responses and Virulence Properties in Pseudomonas aeruginosa

Sex Steroids Induce Membrane Stress Responses and Virulence Properties in Pseudomonas aeruginosa.

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Item Type: Article
Official URL: https://doi.org/10.1128/mBio.01774-20
Journal or Publication Title: mBio
Volume: 11
Number: 5
Date: 2020
Divisions: UTS Centre for Inflammation
Depositing User: General Admin
Identification Number: 10.1128/mBio.01774-20
ISSN: 2150-7511
Date Deposited: 04 Jan 2021 02:30
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.

Creators:
Creators
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Vidaillac, Celine
UNSPECIFIED
Yong, Valerie Fei Lee
UNSPECIFIED
Aschtgen, Marie-Stephanie
UNSPECIFIED
Qu, Jing
UNSPECIFIED
Yang, Shuowei
UNSPECIFIED
Xu, Guangfu
UNSPECIFIED
Seng, Zi Jing
UNSPECIFIED
Brown, Alexandra C.
UNSPECIFIED
Ali, Md Khadem
UNSPECIFIED
Jaggi, Tavleen K.
UNSPECIFIED
Sankaran, Jagadish
UNSPECIFIED
Foo, Yong Hwee
UNSPECIFIED
Righetti, Francesco
UNSPECIFIED
Nedumaran, Anu Maashaa
UNSPECIFIED
Mac Aogáin, Micheál
UNSPECIFIED
Roizman, Dan
UNSPECIFIED
Richard, Jean-Alexandre
UNSPECIFIED
Rogers, Thomas R.
UNSPECIFIED
Toyofuku, Masanori
UNSPECIFIED
Luo, Dahai
UNSPECIFIED
Loh, Edmund
UNSPECIFIED
Wohland, Thorsten
UNSPECIFIED
Czarny, Bertrand
UNSPECIFIED
Horvat, Jay C.
UNSPECIFIED
Hansbro, Philip M.
UNSPECIFIED
Yang, Liang
UNSPECIFIED
Li, Liang
UNSPECIFIED
Normark, Staffan
UNSPECIFIED
Henriques Normark, Birgitta
UNSPECIFIED
Chotirmall, Sanjay H.
UNSPECIFIED
Sperandio, Vanessa
UNSPECIFIED
Last Modified: 04 Jan 2021 02:30
URI: https://eprints.centenary.org.au/id/eprint/778

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