title: The Pseudomonas aeruginosa extracellular secondary metabolite, Paerucumarin, chelates iron and is not localized to extracellular membrane vesicles.
abstract: Proteins encoded by the Pseudomonas aeruginosa pvcA-D operon synthesize a novel isonitrile functionalized cumarin termed paerucumarin. The pvcA-D operon enhances the expression of the P. aeruginosa fimbrial chaperone/usher pathway (cup) genes and this effect is mediated through paerucumarin. Whether pvcA-D and/or paerucumarin affect the expression of other P. aeruginosa genes is not known. In this study, we examined the effect of a mutation in pvcA-D operon the global transcriptome of the P. aeruginosa strain PAO1-UW. The mutation reduced the expression of several ironcontrolled genes including pvdS, which is essential for the expression of the pyoverdine genes. Additional transcriptional studies showed that the pvcA-D operon is not regulated by iron. Exogenously added paerucumarin enhanced pyoverdine production and pvdS expression in PAO1-UW. Iron-chelation experiments revealed that purified paerucumarin chelates iron. However, exogenously added paerucumarin significantly reduced the growth of a P. aeruginosa mutant defective in pyoverdine and pyochelin production. In contrast to other secondary metabolite, Pseudomonas quinolone signal (PQS), paerucumarin is not localized to the P. aeruginosa membrane vesicles. These results suggest that paerucumarin enhances the expression of iron-controlled genes by chelating iron within the P. aeruginosa extracellular environment. Although paerucumarin chelates iron, it does not function as a siderophore. Unlike PQS, paerucumarin is not associated with the P. aeruginosa cell envelope.
authors.affiliation: Departments of Immunology and Molecular Microbiology, Texas Tech University Health Sciences Center, Lubbock, TX, 79430, USA. uzma.sbs@pu.edu.pk.|School of Biological Sciences, University of the Punjab, Lahore, 54590, Pakistan. uzma.sbs@pu.edu.pk.
authors.forename: Uzma
authors.initials: U
authors.lastname: Qaisar
authors.affiliation: Surgery Department, Texas Tech University Health Sciences Center, Lubbock, TX, 79430, USA.
authors.forename: Cassandra J
authors.initials: CJ
authors.lastname: Kruczek
authors.affiliation: Botany Department, Government College University, Faisalabad, 38000, Pakistan.
authors.forename: Muhammed
authors.initials: M
authors.lastname: Azeem
authors.affiliation: School of Biological Sciences, University of the Punjab, Lahore, 54590, Pakistan.
authors.forename: Nasir
authors.initials: N
authors.lastname: Javaid
authors.affiliation: Departments of Immunology and Molecular Microbiology, Texas Tech University Health Sciences Center, Lubbock, TX, 79430, USA.|Medical Education, Texas Tech University Health Sciences Center, Lubbock, TX, 79430, USA.
authors.forename: Jane A
authors.initials: JA
authors.lastname: Colmer-Hamood
authors.affiliation: Departments of Immunology and Molecular Microbiology, Texas Tech University Health Sciences Center, Lubbock, TX, 79430, USA.|Surgery Department, Texas Tech University Health Sciences Center, Lubbock, TX, 79430, USA.
authors.forename: Abdul N
authors.initials: AN
authors.lastname: Hamood
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D000067128:Extracellular Vesicles / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial; D007501:Iron / Q000378:metabolism*; D009154:Mutation; D009842:Oligopeptides / Q000378:metabolism; D009876:Operon; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000378:metabolism*; D064210:Secondary Metabolism
chemical_list: D001426:Bacterial Proteins; D009842:Oligopeptides; C042453:pyoverdin; D007501:Iron
keywords: P. aeruginosa; iron chelation; paerucumarin; siderophore