Sex Hormones Alter Pseudomonas aeruginosa Iron Acquisition and Virulence Factors

Urinary Tract Infections (UTI) are one of the most widespread infections in healthcare and community settings worldwide. Pseudomonas aeruginosa is the third most common pathogen associated with catheter-associated UTI (CAUTI). P. aeruginosa infections are highly resistant and difficult to treat and it is currently classified as priority 1 by the World Health Organisation. In vitro studies of microbes typically employ laboratory media. The inadequacy of nutrient-rich media in simulating the physiological environment has led to the development of multiple media that mimic human body fluids, including Artificial Urine Medium (AUM). By studying growth and in vitro biofilm assays along with proteomics, we sought to establish whether UTI P. aeruginosa respond differently in laboratory media, AUM and urine. To further probe the impact of environmental influences, sex hormones estradiol, progesterone and testosterone were added at physiologically relevant concentrations. The proteomic profiles were then compared between hormone supplemented AUM and urine. Our findings indicate that bacterial responses in standard laboratory media, AUM and urine were distinct. Increased proteins associated with iron acquisition mechanisms were similar in both AUM and urine. However, differences were observed in other virulence and iron pathways, such as phenazine production. Treatment with hormones decreased the abundance of P. aeruginosa proteins involved in iron acquisition. Individual hormones exhibited specific bacterial alterations. The presence of estradiol increased protein abundance of the Pseudomonas Quinolone Signal (PQS) quorum sensing system. This study suggests that P. aeruginosa pathogenesis in UTI infections may be influenced by the presence of specific hormones in the host. Understanding the individual role of host factors could contribute to a personalised treatment approach based on the potential impact on infection susceptibility and outcome.