Lead


Lay summary
Bacterial siderophores (iron chelators) are essential for growth under iron limitation and often qualify as virulence factors. Their production is tightly regulated to assure that they are made only when needed and to avoid a deleterious iron accumulation in the cell. In the Gram-negative opportunistic human pathogen Pseudomonas aeruginosa the expression of the biosynthesis genes for the siderophore pyochelin requires the transcriptional regulator PchR together with pyochelin, which acts as an effector of PchR. Similarly enantio-pyochelin, the optical antipode of pyochelin made by certain plant-beneficial strains of Pseudomonas fluorescens, induces its biosynthesis genes by activating a PchR homolog. The interaction of PchR with its siderophore is stereospecific, meaning that PchR of P. aeruginosa is not activated by enantio-pyochelin, and pyochelin cannot activate PchR of P. fluorescens. Genetic experiments indicate that siderophore recognition occurs in the N-terminal domain of PchR. The objectives of this project are(i) to understand how the different stereochemistry in pyochelin/enantio-pyochelin is generated during biosynthesis(ii) to develop an in vitro assay to investigate binding of the siderophores pyochelin and enantio-pyochelin to their respective PchR proteins(ii) to study the natural occurrence of pyochelin and enantio-pyochelin in pseudomonads and class 2 members of the Burkholderia cepacia complexSignificanceThis project will allow us to understand the importance of chirality in siderophore-mediated iron acquisition.