Sex Steroids Induce Membrane Stress Responses and Virulence Properties in Pseudomonas aeruginosa
Céline Vidaillac, Valerie Fei Lee Yong, Marie‐Stéphanie Aschtgen, Jing Qu, Shuowei Yang, Guangfu Xu, Zi Jing Seng, Alexandra C. Brown, Md Khadem Ali, Tavleen Kaur 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
Abstract
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.