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Mol Microbiol. 2017 Nov;106(4):543-561. doi: 10.1111/mmi.13834. Epub 2017 Oct 10.

Growth of Pseudomonas aeruginosa in zinc poor environments is promoted by a nicotianamine-related metallophore.

Author information

1
Department of Biology, University of Rome Tor Vergata, Rome, Italy.
2
Centro Scienze dell'Invecchiamento e Medicina Traslazionale - CeSI-MeT, Chieti, Italy.
3
Department of Medical, Oral and Biotechnological Sciences, "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy.
4
School of Human and Social Science, "Kore" University of Enna, Enna, Italy.
5
Department of Food Safety and Veterinary Public Health, Istituto Superiore di Sanità, Rome, Italy.

Abstract

Previous studies have suggested that P. aeruginosa possesses redundant zinc uptake systems. To identify uncharacterized zinc transporters, we analyzed the genome-wide transcriptional responses of P. aeruginosa PA14 to zinc restriction. This approach led to the identification of an operon (zrmABCD) regulated by the zinc uptake regulator Zur, that encodes for a metallophore-mediated zinc import system. This operon includes the genes for an uncharacterized TonB-dependent Outer Membrane Protein (ZrmA) and for a putative nicotianamine synthase (ZrmB). The simultaneous inactivation of the ZnuABC transporter and of one of these two genes markedly decreases the ability of P. aeruginosa to grow in zinc-poor media and compromises intracellular zinc accumulation. Our data demonstrate that ZrmB is involved in the synthesis of a metallophore which is released outside the cell and mediates zinc uptake through the ZrmA receptor. We also show that alterations in zinc homeostasis severely affect the ability of P. aeruginosa to cause acute lung and systemic infections in C57BL/6 mice, likely due to the involvement of zinc in the expression of several virulence traits. These findings disclose a hitherto unappreciated role of zinc in P. aeruginosa pathogenicity and reveal that this microorganism can obtain zinc through a strategy resembling siderophore-mediated iron uptake.

PMID:
28898501
DOI:
10.1111/mmi.13834
[Indexed for MEDLINE]
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