Urological metabolic conditions alter regulation of quorum-sensing system and virulence genes expression in uropathogenic Pseudomonasaeruginosa.

Pseudomonas aeruginosa (P. aeruginosa) is responsible for complicated urinary tract infections (UTI) acquired from different transmission routes. Quorum sensing (QS) plays an important role in the regulation of virulence factors in P. aeruginosa and is dependent on the nutritional conditions. Under pathological conditions, urine contains elevated levels of metabolites such as glucose, creatinine, albumin and haem that may alter the QS behavior in P. aeruginosa. Hence, we investigated the role of the QS system in P. aeruginosa on growth and the expression of virulence genes under altered urinary metabolic compositions. We used P. aeruginosa strains isolated from UTI patients, along with PAO1 as a reference strain and grown under simulated metabolic conditions in the synthetic urine. Growth, biofilm formation, motility, siderophore production, rhamnolipid secretion, pyocyanin production, elastase and urease activity were quantified using standard laboratory methods. The expression levels of QS genes, such as lasI/R, rhlI/R, and pqsA/R, alginate synthesis genes (algD/R), the motility-regulating gene (pilA), and urease gene (ureC), were estimated using qRT-PCR for comparison between the growth conditions. The results showed significant differences in growth, biofilm formation and virulence factors between the metabolic conditions and were significantly higher (p<0.001) in simulated glycosuria, haematuria, and creatininuria conditions compared to the control. Under albuminuria, significantly reduced growth and virulence factor production were observed. Compared to control, higher expression levels of lasI/R, rhlI/R, pqsA/R, algD/R, pilA and ureC genes were observed in all conditions except albuminuria. The results highlighted the overexpression of QS-regulating genes and virulence in strains from similar metabolic environments in patients, suggesting possible niche adaptation. Such adaptation may pose considerable challenge in the management of chronic P. aeruginosa infections in urinary tract.