title: Role of the interplay between quorum sensing regulator VqsR and the Pseudomonas quinolone signal in mediating carbapenem tolerance in Pseudomonas aeruginosa.
abstract: Pseudomonas aeruginosa coordinates its response to environmental conditions through activation of a quorum sensing (QS) system. In this study, we investigated the regulatory interaction between the QS transcriptional regulator VqsR and the Pseudomonas quinolone signal (PQS) through integration of sigma factor RpoS, and we addressed whether one of the pathways controlling carbapenem tolerance can be attributed to VqsR. We demonstrate that vqsR expression at the transcriptional level is regulated by pqsA, pqsR, and pqsE. Assessment of the transcriptional expression of vqsR, lasI, rhlI, and qscR in ΔpqsA and ΔpqsAΔrpoS mutants provided insight into pqsA- and rpoS-dependent regulation of vqsR and vqsR-controlled genes. Exogenously supplemented PQS reversed expression of vqsR and vqsR-controlled genes in the ΔpqsA mutant to wild-type levels, but failed to increase expression levels of lasI and qscR in the ΔpqsAΔrpoS mutant to levels observed in wild-type PAO1. The ΔvqsR mutant showed reduced survival when challenged with carbapenems compared to wild-type PAO1. Introduction of a pqsA mutation into the ΔvqsR mutant completely abolished its carbapenem-sensitive phenotype. We conclude that a regulatory link between PQS and vqsR exists, and that RpoS is important in their interaction. We also demonstrate that VqsR affects carbapenem tolerance.
authors.affiliation: Department of Oral Microbiology, Institute of Biomedical Sciences, Tokushima University Graduate School, Kuramoto-cho 3-18-15, Tokushima 770-8504, Japan; Department of Molecular Microbiology, Institute of Health Biosciences, Tokushima University Graduate School, Kuramoto-cho 3-18-15, Tokushima 770-8509, Japan. Electronic address: darija.viducic@gmail.com.
authors.forename: Darija
authors.initials: D
authors.lastname: Viducic
authors.affiliation: Department of Oral Microbiology, Institute of Biomedical Sciences, Tokushima University Graduate School, Kuramoto-cho 3-18-15, Tokushima 770-8504, Japan. Electronic address: kmurakami@tokushima-u.ac.jp.
authors.forename: Keiji
authors.initials: K
authors.lastname: Murakami
authors.affiliation: Department of Oral Microbiology, Institute of Biomedical Sciences, Tokushima University Graduate School, Kuramoto-cho 3-18-15, Tokushima 770-8504, Japan. Electronic address: c301351002@tokushima-u.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Amoh
authors.affiliation: Department of Molecular Microbiology, Institute of Health Biosciences, Tokushima University Graduate School, Kuramoto-cho 3-18-15, Tokushima 770-8509, Japan. Electronic address: tono08@mac.com.
authors.forename: Tsuneko
authors.initials: T
authors.lastname: Ono
authors.affiliation: Department of Oral Microbiology, Institute of Biomedical Sciences, Tokushima University Graduate School, Kuramoto-cho 3-18-15, Tokushima 770-8504, Japan. Electronic address: miyake@tokushima-u.ac.jp.
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Miyake
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D015780:Carbapenems / Q000378:metabolism / Q000494:pharmacology*; D004361:Drug Tolerance; D015964:Gene Expression Regulation, Bacterial; D009154:Mutation; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D015363:Quinolones / Q000378:metabolism* / Q000494:pharmacology; D053038:Quorum Sensing / Q000235:genetics* / Q000502:physiology; D012808:Sigma Factor / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014774:Virulence
chemical_list: C407944:2-heptyl-3-hydroxy-4-quinolone; D001426:Bacterial Proteins; D015780:Carbapenems; D015363:Quinolones; D012808:Sigma Factor; D014157:Transcription Factors; C069567:sigma factor KatF protein, Bacteria
keywords: Antibiotics; Pseudomonas aeruginosa; Quorum sensing; Tolerance