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

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.

• Authors: Celine Vidaillac, Valerie Fei Lee Yong, Marie-Stephanie Aschtgen, Jing Qu, Shuowei Yang, Guangfu Xu, Zi Jing Seng, Alexandra C Brown, Md Khadem Ali, Tavleen K Jaggi, Jagadish Sankaran, Yong Hwee Foo, Francesco Righetti, Anu Maashaa Nedumaran, Micheál Mac Aogáin, Dan Roizman, Jean-Alexandre Richard, Thomas R Rogers, Masanori Toyofuku, Dahai Luo, Edmund Loh, Thorsten Wohland, Bertrand Czarny, Jay C Horvat, Philip M Hansbro, Liang Yang, Liang Li, Staffan Normark, Birgitta Henriques Normark, Sanjay H Chotirmall
• Journal: mBio (mBio) Vol. 11 Issue 5 (09 29 2020) ISSN: 2150-7511 [Electronic] United States
• PMID: 32994320 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Vidaillac et al.

Chemical References

• Alginates
• Gonadal Steroid Hormones
• Testosterone
• Estradiol

Topics

• Alginates (metabolism)
• Animals
• Bacterial Outer Membrane (drug effects)
• Biofilms (drug effects, growth & development)
• Cystic Fibrosis (complications, microbiology)
• Estradiol (chemistry, pharmacology)
• Female
• Gonadal Steroid Hormones (metabolism, pharmacology)
• Humans
• Inflammation
• Male
• Mice
• Mice, Inbred BALB C
• Pseudomonas aeruginosa (genetics, pathogenicity)
• Sex Factors
• Stress, Physiological (drug effects)
• Testosterone (chemistry, pharmacology)
• Virulence