The Pseudomonas aeruginosa extracellular secondary metabolite, Paerucumarin, chelates iron and is not localized to extracellular membrane vesicles

Uzma Qaisar; Cassandra J. Kruczek; Muhammed Azeem; Nasir Javaid; Jane A. Colmer-Hamood; Abdul N. Hamood

doi:10.1007/s12275-016-5645-3

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The Pseudomonas aeruginosa extracellular secondary metabolite, Paerucumarin, chelates iron and is not localized to extracellular membrane vesicles: Uzma Qaisar ^1,2, Cassandra J. Kruczek ³, Muhammed Azeem ⁴, Nasir Javaid ², Jane A. Colmer-Hamood ^1,5, Abdul N. Hamood ^1,3; Journal of Microbiology 2016;54(8):573-581.
DOI: https://doi.org/10.1007/s12275-016-5645-3
Published online: August 2, 2016

¹Departments of Immunology and Molecular Microbiology, Texas Tech University Health Sciences Center, Lubbock, TX79430, USA, ²School of Biological Sciences, University of the Punjab, Lahore, 54590, Pakistan, ³Surgery Department, Texas Tech University Health Sciences Center, Lubbock, TX79430, USA, ⁴Botany Department, Government College University, Faisalabad 38000, Pakistan, ⁵Medical Education, Texas Tech University Health Sciences Center, Lubbock, TX79430, USA¹Departments of Immunology and Molecular Microbiology, Texas Tech University Health Sciences Center, Lubbock, TX79430, USA, ²School of Biological Sciences, University of the Punjab, Lahore, 54590, Pakistan, ³Surgery Department, Texas Tech University Health Sciences Center, Lubbock, TX79430, USA, ⁴Botany Department, Government College University, Faisalabad 38000, Pakistan, ⁵Medical Education, Texas Tech University Health Sciences Center, Lubbock, TX79430, USA

Corresponding author: Uzma Qaisar , Tel: +92-30-42611-611,

Received: 31 December 2015 • Revised: 31 May 2016 • Accepted: 1 July 2016

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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.

Keywords: P. aeruginosa;paerucumarin;iron chelation;siderophore

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The Pseudomonas aeruginosa extracellular secondary metabolite, Paerucumarin, chelates iron and is not localized to extracellular membrane vesicles

J. Microbiol. 2016;54(8):573-581. Published online August 2, 2016

DOI: https://doi.org/10.1007/s12275-016-5645-3

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