title: Quorum-sensing-deficient (lasR) mutants emerge at high frequency from a Pseudomonas aeruginosa mutS strain.
abstract: In Pseudomonas aeruginosa, quorum sensing constitutes a highly complex cell-to-cell communication system that, along with the cognate acylhomoserine lactone signals and regulators LasR and RhlR, modulates the production of virulence factors and a wide range of metabolic functions. In a previous paper, the authors reported that mismatch repair disruption in P. aeruginosa results in the spontaneous and reproducible emergence of defined morphological colony variants after a relatively short period of cultivation in an aerated rich medium, in contrast to the non-mutator parental strain, which does not display any kind of diversification under identical incubation conditions. One of the morphotypical variants, mS2, emerges at a high frequency and displays differences in virulence traits that could be regulated by major quorum-sensing regulators. The present study shows that mutS mS2 variants had defective LasR function due to simple but different point mutations along the lasR gene sequence, indicating that LasR inactivation is the main cause of mS2 phenotypic diversification. Moreover, it was determined that a non-functional LasR would confer a selective advantage in the late stationary phase, since viability was notably higher for mS2. Interestingly, in all mS2 variants analysed, no sequence alterations were found in the gacA and rhlR genes, suggesting that the selective pressures for GacA/RhlR and LasR were not the same and differed from those in other Pseudomonas species, which, when incubated in nutrient-rich liquid stationary-phase cultures, show specific high instability in the gacA-gacS genes.
authors.affiliation: Centro de Investigaciones en Química Biológica de Córdoba, CONICET, Departamento de Química Biológica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Haya de la Torre y Medina Allende, Ciudad Universitaria, X5000HUA, Córdoba, Argentina.
authors.forename: Adela M
authors.initials: AM
authors.lastname: Luján
authors.forename: Alejandro J
authors.initials: AJ
authors.lastname: Moyano
authors.forename: Ignacio
authors.initials: I
authors.lastname: Segura
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Argaraña
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Smania
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics*; D017173:Caenorhabditis elegans / Q000382:microbiology; D004268:DNA-Binding Proteins / Q000235:genetics*; D014644:Genetic Variation; D008969:Molecular Sequence Data; D051719:MutS DNA Mismatch-Binding Protein / Q000172:deficiency* / Q000235:genetics*; D017354:Point Mutation; D011550:Pseudomonas aeruginosa / Q000235:genetics* / Q000472:pathogenicity; D053038:Quorum Sensing / Q000235:genetics*; D015534:Trans-Activators / Q000235:genetics*; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C080365:LasR protein, Pseudomonas aeruginosa; D015534:Trans-Activators; D051719:MutS DNA Mismatch-Binding Protein