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

Maria Chiara Mastropasqua, Melania D'Orazio, Mauro Cerasi, Francesca Pacello, Angelo Gismondi, Antonella Canini, Lorena Canuti, Ada Consalvo, Domenico Ciavardelli, Barbara Chirullo, Paolo Pasquali, Andrea Battistoni

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)543-561
Number of pages19
JournalMolecular Microbiology
Volume106
Issue number4
DOIs
Publication statusPublished - Nov 1 2017

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

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