Host suppression of quorum sensing during catheter-associated urinary tract infections

Nat Commun. 2018 Oct 25;9(1):4436. doi: 10.1038/s41467-018-06882-y.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acyl-Butyrolactones / pharmacology
  • Animals
  • Catheter-Related Infections / microbiology*
  • Catheter-Related Infections / pathology
  • DNA, Bacterial / metabolism
  • Gene Expression Regulation, Bacterial / drug effects
  • Host-Pathogen Interactions* / drug effects
  • Humans
  • Mice
  • Phenotype
  • Pseudomonas Infections / microbiology
  • Pseudomonas Infections / pathology
  • Pseudomonas aeruginosa / drug effects
  • Quorum Sensing* / drug effects
  • Quorum Sensing* / genetics
  • Sequence Analysis, RNA
  • Urea / pharmacology
  • Urinary Tract Infections / microbiology*
  • Urinary Tract Infections / pathology

Substances

  • Acyl-Butyrolactones
  • DNA, Bacterial
  • Urea