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Anaerobiosis-induced loss of cytotoxicity is due to inactivation of quorum sensing in Pseudomonas aeruginosa

 Kang-Mu Lee  ;  Mi Young Yoon  ;  Yongjin Park  ;  Joon-Hee Lee  ;  Sang Sun Yoon 
 INFECTION AND IMMUNITY, Vol.79(7) : 2792-2800, 2011 
Journal Title
Issue Date
Anaerobiosis ; Bacterial Proteins/genetics ; Bacterial Proteins/metabolism* ; Blotting, Western ; Cell Line, Tumor ; Epithelial Cells/microbiology* ; Gene Expression Regulation, Bacterial ; Genes, Reporter ; Humans ; Metalloendopeptidases/genetics ; Metalloendopeptidases/metabolism* ; Pancreatic Elastase/genetics ; Pancreatic Elastase/metabolism ; Plasminogen Activator Inhibitor 1/metabolism ; Plasminogen Activator Inhibitor 1/pharmacology ; Plasminogen Activator Inhibitor 2/metabolism ; Plasminogen Activator Inhibitor 2/pharmacology ; Polymerase Chain Reaction ; Pseudomonas Infections ; Pseudomonas aeruginosa/genetics ; Pseudomonas aeruginosa/growth & development ; Pseudomonas aeruginosa/pathogenicity* ; Quinolones/metabolism ; Quinolones/pharmacology ; Quorum Sensing* ; Virulence Factors/genetics ; Virulence Factors/metabolism
Pseudomonas aeruginosa, an opportunistic pathogen of clinical importance, causes chronic airway infections in patients with cystic fibrosis (CF). Current literature suggests that pockets with reduced oxygen tension exist in the CF airway mucus. However, virulence features of this opportunistic pathogen under such conditions are largely unknown. Cell-free supernatant of the standard laboratory P. aeruginosa strain PAO1 obtained from anaerobic culture, but not aerobic culture, failed to kill A549 human airway epithelial cells. Further investigation revealed that this reduced cytotoxicity upon anaerobiosis was due to the suppressed secretion of elastase, a virulence factor controlled by P. aeruginosa quorum sensing (QS). Both a lacZ-reporter fusion assay and quantitative real-time PCR (RT-PCR) analysis demonstrated that transcription of the elastase-encoding lasB gene was substantially decreased during anaerobic growth compared with aerobic growth. Moreover, transcription of other genes controlled by the LasI/R QS system, such as rhlR, vqsR, mvfR, and rsaL, was also repressed under the same anaerobic growth conditions. Importantly, synthesis of 3-oxo-C(12)-HSL (PAI-1), an autoinducer molecule that mediates induction of the LasI/R QS system, was >22-fold decreased during anaerobic growth while C(4)-HSL (PAI-2), which mediates RhlI/R QS, was nondetectable under the same growth conditions. Transcription of the lasB gene was restored by exogenous supplementation with autoinducers, with PAI-2 more effective than PAI-1 or Pseudomonas quinolone signal (PQS) at restoring transcription of the lasB gene. Together, these results suggest that anaerobiosis deprives P. aeruginosa of the ability to regulate its virulence via QS and this misregulation attenuates the pathogenic potential of this important pathogen.
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1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Park, Yong Jin(박용진)
Yoon, Sang Sun(윤상선) ORCID logo https://orcid.org/0000-0003-2979-365X
Lee, Kang Mu(이강무) ORCID logo https://orcid.org/0000-0001-7414-5921
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