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

mBio

Thorsten Wohland¹  Jagadish Sankaran¹  Thomas R. Rogers²  Francesco Righetti³  Guangfu Xu⁴  Shuowei Yang⁴  Masanori Toyofuku⁵  Jean-Alexandre Richard⁶  Tavleen K. Jaggi⁷  Micheál Mac Aogáin⁷  Marie-Stephanie Aschtgen⁷  Valerie Fei Lee Yong⁷  Dahai Luo⁷  Celine Vidaillac⁷  Staffan Normark⁷  Birgitta Henriques-Normark⁷  Bertrand Czarny⁷  Sanjay H. Chotirmall⁷  Md Khadem Ali⁸  Jay C. Horvat⁸  Alexandra C. Brown⁸  Philip M. Hansbro⁸  Anu Maashaa Nedumaran⁹  Liang Li^1,10  Jing Qu^1,10  Yong Hwee Foo^1,11  Edmund Loh^1,11  Zi Jing Seng^1,11  Liang Yang^1,11  Dan Roizman^1,11 

[1] Department of Biological Sciences, National University of Singapore, Singapore;Department of Clinical Microbiology, Trinity College Dublin, St. James’s Hospital Campus, Dublin, Ireland;Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden;Department of Otolaryngology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong, China;Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Japan;Functional Molecules and Polymers, Institute of Chemical and Engineering Sciences, ICES, Agency for Science, Technology, and Research, A*STAR, Singapore;Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore;Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute, Newcastle, New South Wales, Australia;School of Materials Science and Engineering (MSE), Nanyang Technological University, Singapore;Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, Guangdong, China;Singapore Centre for Environmental Life Sciences Engineering, Nanyang Technological University, Singapore;

关键词: hormones;    steroids;    Pseudomonas aeruginosa;    membrane stress;    gender;   

DOI  :  10.1128/mBio.01774-20

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown