Chronic bacterial infections on medical devices, including catheter-associated urinary tract infections (CAUTI), are associated with bacterial biofilm communities that are refractory to antibiotic therapy and resistant to host immunity. Previously, we have shown that Pseudomonas aeruginosa can cause CAUTI by forming a device-associated biofilm that is independent of known biofilm exopolysaccharides. Here, we show by RNA-seq that host urine alters the transcriptome of P. aeruginosa by suppressing quorum sensing regulated genes. P. aeruginosa produces acyl homoserine lactones (AHLs) in the presence of urea, but cannot perceive AHLs. Repression of quorum sensing by urine implies that quorum sensing should be dispensable during infection of the urinary tract. Indeed, mutants defective in quorum sensing are able to colonize similarly to wild-type in a murine model of CAUTI. Quorum sensing-regulated processes in clinical isolates are also inhibited by urea. These data show that urea in urine is a natural anti-quorum sensing mechanism in mammals.
Nature communications. 2018 Oct 25*** epublish ***
Stephanie J Cole, Cherisse L Hall, Maren Schniederberend, John M Farrow Iii, Jonathan R Goodson, Everett C Pesci, Barbara I Kazmierczak, Vincent T Lee
Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, College Park, MD, 20742, USA., Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT, 06520, USA., Department of Microbiology and Immunology, The Brody School of Medicine at East Carolina University, Greenville, 27834, NC, USA., Department of Cell Biology and Molecular Genetics, University of Maryland, College Park, College Park, MD, 20742, USA. .