Characterization of N-butanoyl-L-homoserine lactone (C4-HSL) deficient clinical isolates of Pseudomonas aeruginosa

Microb Pathog. 2008 Jan;44(1):13-9. doi: 10.1016/j.micpath.2007.06.005. Epub 2007 Jul 4.


In the opportunistic pathogen Pseudomonas aeruginosa, the production of several virulence factors such as elastase, rhamnolipids and pyocyanin depends on cell-to-cell signaling or quorum sensing (QS) involving N-acylhomoserine lactone (AHL) signal molecules. In vitro studies with laboratory strains and virulence studies in animals with these same strains have demonstrated the contribution of QS to the pathogenesis of P. aeruginosa. However, the importance of P. aeruginosa QS systems in the development of human infections is not clearly known. In order to determine if deficiency within the QS system compromises the ability of P. aeruginosa to cause infections in humans, we collected 50 P. aeruginosa clinical isolates. Phenotypic characterization showed that isolates I-457, I-458, I-459 and I-461 were defective in the production of N-butanoyl-l-homoserine lactone (C4-HSL) signaling molecule and virulence factors elastase, protease, pyocyanin and rhamnolipids. Analysis of the sequences of the lasR, lasI, rhlR and rhlI genes of these four isolates showed that two of the four isolates had mutational defects in both rhlR and rhlI genes while other two isolates were only mutated in the rhlI gene. The combination of rhlR and rhlI mutations or only rhlI mutation probably explains their C4-HSL and virulence factors deficiencies. These observations suggest that QS deficient P. aeruginosa clinical isolates are able to cause infections and that in addition to known virulence factors, factors yet unidentified may contribute to the pathogenesis of P. aeruginosa.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Butyrolactone / analogs & derivatives*
  • 4-Butyrolactone / genetics
  • Bacterial Proteins / genetics
  • Humans
  • Ligases / genetics
  • Movement / physiology
  • Mutation / genetics
  • Mutation / physiology*
  • Pseudomonas Infections / microbiology*
  • Pseudomonas aeruginosa / genetics*
  • Pseudomonas aeruginosa / growth & development
  • Pseudomonas aeruginosa / pathogenicity*
  • Quorum Sensing / genetics
  • Quorum Sensing / physiology
  • Transcription Factors / genetics
  • Virulence Factors / analysis


  • Bacterial Proteins
  • N-butyrylhomoserine lactone
  • RhlR protein, Pseudomonas aeruginosa
  • Transcription Factors
  • Virulence Factors
  • Ligases
  • RHLI protein, Pseudomonas aeruginosa
  • 4-Butyrolactone