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Infect. Immun. doi:10.1128/IAI.00559-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

The high affinity Zn²⁺ uptake system ZnuABC is required for bacterial zinc homeostasis in intracellular environments and contributes to virulence of Salmonella enterica

Department of Biology, University of Rome Tor Vergata, 00133 Rome, Italy; Department of Food Safety and Veterinary Public Health, Istituto Superiore di Sanità, 00161 Rome, Italy, Research Center, IRCCS San Raffaele "La Pisana", 00163, Rome, Italy

^* To whom correspondence should be addressed. Email: andrea.battistoni{at}uniroma2.it.

	Abstract

To investigate the relevance of zinc in the host-pathogen interaction we have constructed Salmonella enterica mutant strains deleted of the znuA gene which encodes for the periplasmic component of the ZnuABC high affinity Zn²⁺ transporter. This mutation does not alter Salmonella ability to grow in rich media, but drastically reduces bacterial ability to multiply in media deprived of zinc. In agreement with this phenotype, ZnuA accumulates only in bacteria cultivated in environments poor of zinc. In spite of the nearly millimolar intracellular concentration of zinc, we have found that znuA is highly expressed in intracellular salmonellae recovered either from cultivated cells or from the spleens of infected mice. We have also observed that znuA mutants are impaired in their ability to grow in Caco-2 epithelial cells and that bacteria starved for zinc display decreased ability to multiply in phagocytes. A dramatic reduction in pathogenicity of the znuA mutants was observed either in Salmonella susceptible (Balb/c) or Salmonella resistant (DBA-2) mice, infected intraperitoneally or orally. This study shows that the free metal quota available for bacterial growth within the infected animal is limited, despite its apparent elevated concentration within cells and in plasma and suggests that Salmonella exploits ZnuABC zinc transporter for maximizing zinc availability in such conditions. These results shed new light on the complex functions of zinc in vertebrate and bacterial physiology and paw the way for a better comprehension of pathogenic mechanisms in Salmonella infections.

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