title: QsrO a novel regulator of quorum-sensing and virulence in Pseudomonas aeruginosa.
abstract: In Pseudomonas aeruginosa, the production of many secreted virulence factors is controlled by a quorum-sensing (QS) circuit, constituted of transcriptional activators (LasR, RhlR, PqsR) and their cognate signaling molecules (3-oxo-C12-HSL, C4-HSL, PQS). QS is a cooperative behavior that is beneficial to a population but can be exploited by "QS-cheaters", individuals which do not respond to the QS-signal, but can use public goods produced by QS-cooperators. In order to identify QS-deficient clones we designed a genetic screening based on a lasB-lacZ fusion. We isolated one clone (PT1617) deficient in QS-dependent gene expression and virulence factor production despite wild type lasR, rhlR and pqsR alleles. Whole genome sequencing of PT1617 revealed a 3,552 bp deletion encompassing ORFs PA2228-PA2229-PA2230 and the pslA gene. However, complementation of PT1617 by plasmid-encoded copies of these ORFs, did not restore QS. Unexpectedly, gene expression levels of ORFs PA2228, PA2227 (vqsM) and PA2222, located adjacent to the deletion, were 10 to 100 fold higher in mutant PT1617 than in PAO1. When expressed from a constitutive promoter on a plasmid, PA2226, alone was found to be sufficient to confer a QS-negative phenotype on PAO1 as well as on PA14. Co-expression of PA2226 and PA2225 in PAO1 further prevented induction of the type III secretion system. In summary, we have identified a novel genetic locus including ORF2226 termed qsrO (QS-repressing ORF), capable of down-regulating all three known QS-systems in P. aeruginosa.
authors.affiliation: Departement of Microbiology and Molecular Medicine, University of Geneva, Geneva, Switzerland ; Service of Infectious Diseases, University Hospitals Geneva, Geneva, Switzerland.
authors.forename: Thilo
authors.initials: T
authors.lastname: Köhler
authors.affiliation: Department of Physiology and Metabolism, University of Geneva, Geneva, Switzerland.
authors.forename: Hajer
authors.initials: H
authors.lastname: Ouertatani-Sakouhi
authors.affiliation: Department of Physiology and Metabolism, University of Geneva, Geneva, Switzerland.
authors.forename: Pierre
authors.initials: P
authors.lastname: Cosson
authors.affiliation: Departement of Microbiology and Molecular Medicine, University of Geneva, Geneva, Switzerland ; Service of Infectious Diseases, University Hospitals Geneva, Geneva, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: van Delden
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D058947:Bacterial Secretion Systems / Q000235:genetics; D001483:Base Sequence; D015964:Gene Expression Regulation, Bacterial; D005816:Genetic Complementation Test; D016680:Genome, Bacterial; D059014:High-Throughput Nucleotide Sequencing; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D010957:Plasmids; D011401:Promoter Regions, Genetic; D011550:Pseudomonas aeruginosa / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D053038:Quorum Sensing / Q000235:genetics*; D017384:Sequence Deletion; D015398:Signal Transduction; D014774:Virulence; D037521:Virulence Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems; D037521:Virulence Factors