The impact of testosterone on Pseudomonas aeruginosa pathogenicity and antimicrobial susceptibility

Abstract

Introduction:Pseudomonas aeruginosa (PA) has a key role in the pathogenesis of cystic fibrosis (CF) and non-CF related bronchiectasis. Female sex steroid hormones, such as estrogen influence microbial virulence. The role of testosterone, however, remains uncertain. Methods:Pseudomonas swarming and surfing motility were assessed using a testosterone pre-exposed (25nM to 1mM) laboratory strain (PAO1). 3D architecture (surface roughness ratio, RR) and physicochemical properties (antimicrobial efficacy) of biofilms grown under the influence of hormones were characterized by confocal and light sheet microscopy. Time-kill assays were concurrently performed. Results: Testosterone exposure significantly altered PA surface motility in a concentration dependent manner. Biofilms grown under testosterone enriched conditions were flatter (RR=0.94) and less diffusible as compared to control (RR=0.82). The killing effects of major anti-pseudomonal antibiotics, colistin and tobramycin were enhanced (35% and 90%, respectively) against biofilms grown in the presence of testosterone. Conclusion: Testosterone influences PA virulence and antimicrobial susceptibility in a concentration dependent manner. Unraveling molecular mechanisms by which testosterone interacts with PA is now required to assess the clinical significance of these findings. Funding: This research is supported by the Lee Kong Chian School of Medicine, Nanyang Technological University Start-Up Grant.