Growth of Pseudomonas aeruginosa in zinc poor environments is promoted by a nicotianamine‐related metallophore. Issue 4 (10th October 2017)

• Record Type: Journal Article
• Authors: Mastropasqua, Maria Chiara; D'Orazio, Melania; Cerasi, Mauro; Pacello, Francesca; Gismondi, Angelo; Canini, Antonella; Canuti, Lorena; Consalvo, Ada; Ciavardelli, Domenico; Chirullo, Barbara; Pasquali, Paolo; Battistoni, Andrea
• Is Part Of: Molecular microbiology. Volume 106:Issue 4(2017)
• Page Start: 543
• Page End: 561
• Publication Date: 2017-10-10
• Subjects: Molecular microbiology -- Periodicals; 572.829
• DOI: 10.1111/mmi.13834
• Languages: English
• ISSNs: 0950-382X

Abstract

Summary: 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. Abstract : P . aeruginosa is equipped with redundant mechanisms for the acquisition of Zn in environments poor of this metal. Here we characterize a previously unrecognized Zn‐import system (ZrmABCD) that relies on the release of a metallophore structurally related to nicotianamine. Alteration in zinc‐importing ability caused by deletion of the major components of the Zn‐uptake apparatus (ZnuA or ZrmA) has a crucial impact on the expression of several virulence features and on the ability of P . aeruginosa to cause infections in mice.