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Thesis

French

ID: <

10670/1.05v137

>

Where these data come from
Nicotianamine-like metallophores in bacteria : regulation, diversity, and evolution

Abstract

Some metals are essential nutrients because they participate in vital cellular processes. In excess, however, they can have deleterious effects. It is therefore crucial to keep their concentration tightly controlled. In plants, nicotianamine (NA) contributes to this maintenance of equilibrium thanks to its ability to fix and transport metals. This metallophore is also produced by fungi and an analogue has been identified from an archaeon. Recently, bacterial derivatives have been characterized in Staphylococcus aureus, Pseudomonas aeruginosa and Yersinia pestis, which synthesize staphylopine (Sp), pseudopaline (Pp) and yersinopine (Yp), respectively. In this work, the regulation, diversity, and evolution of NA-type bacterial metallophores have been explored using a multidisciplinary approach combining microbiology, biochemistry, bioinformatics, and analytical chemistry. By establishing rules to predict the nature of the metallophores produced, a new homologue called bacillopaline has been discovered. The study of Sp synthesis in S. aureus has revealed an original post-translational regulation by metals. In P. aeruginosa, the study of the transport pathways of Pp has unraveled the use of an efflux pump, insofar never associated with the cnt system, as well as a periplasmic modification of the metallophore involved in its import. The role of the cnt operon has been compared in two species of the genus Yersinia in which the biosynthesis of Yp has been demonstrated. In A. mirum, the modification of Sp by a methyltransferase has been described. Finally, the diversity and the evolutionary history of NA-type systems have been discussed.

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