Pseudopaline, a staphylopine-like metallophore involved in zinc and nickel uptake in Pseudomonas aeruginosa

28 Metal uptake is vital for all living organisms. In metal scarce conditions, a common bacterial 29 strategy consists in the biosynthesis of metallophores, their export in the extracellular medium 30 and the recovery of a metal-metallophore complex through dedicated membrane transporters. 31 Staphylopine is a recently described metallophore distantly related to plant nicotianamine that 32 contributes to the broad-spectrum metal uptake capabilities of Staphylococcus aureus. Here, 33 we characterize a four genes operon (PA4837–PA4834) in Pseudomonas aeruginosa involved 34 in the biosynthesis and trafficking of a staphylopine-like metallophore named pseudopaline. 35 Pseudopaline differs from staphylopine with regard to the stereochemistry of its histidine 36 moiety associated to an alpha ketoglutarate moiety instead of pyruvate. In vivo, the 37 pseudopaline operon is regulated by zinc through the Zur repressor. The metal-uptake 38 property of the pseudopaline system appears different from that of staphylopine with a 39 predominant effect on nickel uptake, and on zinc uptake in metal scarce conditions mimicking 40 a chelating environment, thus reconciling the regulation of the cnt operon by zinc with its 41 function as a zinc importer under metal scarce conditions. 42 43 AUTHOR SUMMARY 44 Zinc is an essential micronutrients for bacteria, particularly important at the host-pathogen 45 interface where the host tends to sequester metals in a so called nutritional immunity 46 framework, and the pathogenic bacterium increases its metal uptake efforts in order to keep 47 up with its metal requirements. Here we reveal a novel metallophore, named pseudopaline, 48 which is synthesized and exported by Pseudomonas aeruginosa and serves for the uptake of 49 nickel in metal poor media, and for the uptake of zinc in metal scarce conditions that mimic 50 the chelating environment that presumably prevails within a host. 51 52 not peer-reviewed) is the author/funder. All rights reserved. No reuse allowed without permission. The copyright holder for this preprint (which was . http://dx.doi.org/10.1101/165571 doi: bioRxiv preprint first posted online Jul. 19, 2017;