title: Burkholderia pseudomallei kynB plays a role in AQ production, biofilm formation, bacterial swarming and persistence.
abstract: Kynurenine formamidase (KynB) forms part of the kynurenine pathway which metabolises tryptophan to anthranilate. This metabolite can be used for downstream production of 2-alkyl-4-quinolone (AQ) signalling molecules that control virulence in Pseudomonas aeruginosa. Here we investigate the role of kynB in the production of AQs and virulence-associated phenotypes of Burkholderia pseudomallei K96243, the causative agent of melioidosis. Deletion of kynB resulted in reduced AQ production, increased biofilm formation, decreased swarming and increased tolerance to ciprofloxacin. Addition of exogenous anthranilic acid restored the biofilm phenotype, but not the persister phenotype. This study suggests the kynurenine pathway is a critical source of anthranilate and signalling molecules that may regulate B. pseudomallei virulence.
authors.affiliation: Biosciences, College of Life and Environmental Sciences, University of Exeter, Exeter, UK. Electronic address: a.t.butt@sheffield.ac.uk.
authors.forename: Aaron
authors.initials: A
authors.lastname: Butt
authors.affiliation: Centre for Biomolecular Sciences, School of Biosciences, University of Nottingham, Nottingham, UK. Electronic address: nigel.halliday@nottingham.ac.uk.
authors.forename: Nigel
authors.initials: N
authors.lastname: Halliday
authors.affiliation: Centre for Biomolecular Sciences, School of Biosciences, University of Nottingham, Nottingham, UK. Electronic address: paul.williams@nottingham.ac.uk.
authors.forename: Paul
authors.initials: P
authors.lastname: Williams
authors.affiliation: Defence Science and Technology Laboratory, Porton Down, Salisbury, UK. Electronic address: HSAtkins@mail.dstl.gov.uk.
authors.forename: Helen S
authors.initials: HS
authors.lastname: Atkins
authors.affiliation: Department of Immunology and Infection, Faculty of Infectious & Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK. Electronic address: gregory.bancroft@lshtm.ac.uk.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Bancroft
authors.affiliation: Biosciences, College of Life and Environmental Sciences, University of Exeter, Exeter, UK. Electronic address: r.w.titball@exeter.ac.uk.
authors.forename: Richard W
authors.initials: RW
authors.lastname: Titball
mesh_terms: D005558:Arylformamidase / Q000378:metabolism*; D018441:Biofilms / Q000254:growth & development*; D016957:Burkholderia pseudomallei / Q000201:enzymology* / Q000235:genetics / Q000502:physiology*; D017353:Gene Deletion; D008124:Locomotion; D015363:Quinolones / Q000378:metabolism*; D015398:Signal Transduction; D014364:Tryptophan / Q000378:metabolism; D014774:Virulence; D062367:ortho-Aminobenzoates / Q000378:metabolism
chemical_list: D015363:Quinolones; D062367:ortho-Aminobenzoates; C031385:anthranilic acid; D014364:Tryptophan; D005558:Arylformamidase
keywords: Anthranilate; Antibiotic tolerance; Kynurenine; Quorum sensing; Virulence factors