Siderophore-mediated zinc acquisition enhances enterobacterial colonization of the inflamed gut

Abstract

Zinc is an essential cofactor for bacterial metabolism, and many Enterobacteriaceae express the zinc transporters ZnuABC and ZupT to acquire this metal in the host. Unexpectedly, the probiotic bacterium Escherichia coli Nissle 1917 exhibited appreciable growth in zinc-limited media even when these transporters were deleted. By utilizing in vitro and in vivo studies, as well as native spray metal infusion mass spectrometry and ion identity molecular networking, we discovered that Nissle utilizes yersiniabactin as a zincophore. Indeed, yersiniabactin enables Nissle to scavenge zinc in zinc-limited media, to resist calprotectin-mediated zinc sequestration, and to thrive in the inflamed gut. Moreover, we discovered that yersiniabactin’s affinity for iron or zinc changes in a pH-dependent manner, with higher affinity for zinc as the pH increased. Altogether, we demonstrate that siderophore metal affinity can be influenced by the local environment and reveal a mechanism of zinc acquisition available to many commensal and pathogenic Enterobacteriaceae.

Zinc is an important inter-kingdom signal between the host and microbe

“…Although deletion of the zur gene does not affect the virulence of Staphylococcus aureus (S. aureus) and Mycobacterium tuberculosis (M. tuberculosis), it decreases the mortality of mice infected with STm [32][33][34]. Under zinc-limiting conditions, the growth of E. coli Nissle 1917 did not weaken due to the deletion of zinc transporter genes, and the bacteria utilize yersiniabactin to scavenge zinc to resist calprotectin-mediated zinc sequestration in the inflamed gut [35]. The newly discovered TonB-dependent outer membrane protein receptor ZnuD in Neisseria meningitidis regulates the absorption of zinc and haem and can induce antibodies combined with vesicles to infect guinea pigs and activate complement-mediated cytotoxicity to kill bacteria [36,37].…”

Pathophysiology and Molecular Imaging of Diabetic Foot Infections

“…Iron is an essential cofactor for respiration and central metabolism. Zinc is the catalytic center for many enzymes and is required for 5-6% of all protein functions [158]. Siderophores are often categorized into the following groups according to the chemical moiety that binds iron: catecholates, hydroxamates, and carboxylates.…”

“…Mixed type siderophores have two or more of these moieties. Siderophores may actively alter their affinity for iron in order to bind other metals by increasing their expression of metal transporters [158]. Desferricoprogen-a natural siderophore produced by Penicillium chrysogenum and Neurospora crass-reportedly bound to both trivalent (Al(III) and In(III)) or divalent (Cu(II), Ni(II), Zn(II), and Fe(II) metal ions [159].…”