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Pyochelin-mediated signalling in Pseudomonas

English title Pyochelin-mediated signalling in Pseudomonas
Applicant Reimmann Cornelia
Number 113955
Funding scheme Project funding
Research institution Département de Microbiologie Fondamentale Faculté de Biologie et de Médecine Université de Lausanne
Institution of higher education University of Lausanne - LA
Main discipline Experimental Microbiology
Start/End 01.04.2007 - 30.09.2010
Approved amount 260'000.00
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Keywords (6)

Pseudomonas; iron uptale; siderophore; pyochelin; AraC-type regulator; RsmA

Lay Summary (English)

Lead
Lay summary
Iron is an essential element for most living organisms, including bacteria. Despite its abundance on earth, it is not freely available to microorganisms under aerobic conditions, as it forms poorly soluble ferric hydroxides in the environment or is tightly bound to transport and storage proteins in mammalian hosts. Iron can also be deleterious to the cell because it catalyses the generation of hydroxyl radicals through the Fenton reaction. Iron acquision and storage thus need to be controlled very carefully to avoid both iron shortage and iron overload. To acquire iron, bacteria have evolved several strategies, the most common involves high affinity iron-chelating molecules, termed siderophores.
Pyochelin, the siderophore which is the focus of this project, is made by the Gram-negative bacterium Pseudomonas aeruginosa where it contributes to the virulence of this opportunistic human pathogen. Pyochelin biosynthesis and uptake genes, which are clustered in the P. aeruginosa chromosome, are repressed by the Fur protein under iron-replete conditions, and induced when iron is limiting and pyochelin is present in the extracellular environment. Induction requires pyochelin uptake proteins such as the outer membrane receptor FptA and the inner membrane permease FptX, as well as PchR, a regulatory protein of the AraC/XylS family. Upon interaction with the siderophore, PchR binds to conserved sequence elements of target genes and regulates their transcription.
Pyochelin is the first siderophore reported to interact with an AraC-type regulator. During this project we will investigate several aspects of this interaction. We will characterize the functional domains of PchR involved in effector recognition, multimerization, and DNA binding and we will isolate pyochelin-independent (constitutive) PchR mutants.
A second part of the project focuses on the regulation of pyochelin-mediated iron uptake which has been studied so far on the transcriptional level only. We now have evidence for an important post-transcriptional control, both in P. aeruginosa and in the related bacterium Pseudomonas fluorescens The molecular mechanism of this regulation will be studied.
This project will increase our understanding of transcriptional and post-transcriptional control of pyochelin biosynthesis in Pseudomonas sp.and allow us to characterize a so far unique interaction between a siderophore and its AraC-type regulator.
Direct link to Lay Summary Last update: 21.02.2013

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Associated projects

Number Title Start Funding scheme
102174 Role and regulation of the Pseudomonas aeruginosa siderophore pyochelin and its uptake system 01.01.2004 Project funding
132998 Enantio-pyochelin: Biosynthesis, regulation, and natural occurrence 01.12.2010 Project funding

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