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A comprehensive approach was used to identify novel targets of NO\u00b7 in\n            <jats:named-content content-type=\"genus-species\">Salmonella enterica<\/jats:named-content>\n            serovar Typhimurium (\n            <jats:italic>S.<\/jats:italic>\n            \u00a0Typhimurium). Newly identified targets include zinc metalloproteins required for DNA replication and repair (DnaG, PriA, and TopA), protein synthesis (AlaS and RpmE), and various metabolic activities (ClpX, GloB, MetE, PepA, and QueC). The cytotoxic actions of free zinc are mitigated by the ZntA and ZitB zinc efflux transporters, which are required for\n            <jats:italic>S.<\/jats:italic>\n            \u00a0Typhimurium resistance to zinc overload and nitrosative stress\n            <jats:italic>in vitro<\/jats:italic>\n            . Zinc efflux also ameliorates NO\u00b7-dependent zinc mobilization following internalization by activated macrophages and is required for virulence in NO\u00b7-producing mice, demonstrating that host-derived NO\u00b7 causes zinc stress in intracellular bacteria.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Nitric oxide (NO\u00b7) is produced by macrophages in response to inflammatory stimuli and restricts the growth of intracellular bacteria. Mechanisms of NO\u00b7-dependent antimicrobial actions are incompletely understood. Here, we show that zinc metalloproteins are important targets of NO\u00b7 in\n            <jats:italic>Salmonella<\/jats:italic>\n            , including the DNA replication proteins DnaG and PriA, which were hypothesized to be NO\u00b7 targets in earlier studies. Like iron, zinc is a cofactor for several essential proteins but is toxic at elevated concentrations. This study demonstrates that NO\u00b7 mobilizes free zinc in\n            <jats:italic>Salmonella<\/jats:italic>\n            and that specific efflux transporters ameliorate the cytotoxic effects of free zinc during infection.\n          <\/jats:p>","DOI":"10.1128\/mbio.01040-18","type":"journal-article","created":{"date-parts":[[2018,8,13]],"date-time":"2018-08-13T07:14:41Z","timestamp":1534144481000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":41,"title":["Nitric Oxide Disrupts Zinc Homeostasis in Salmonella enterica Serovar Typhimurium"],"prefix":"10.1128","volume":"9","author":[{"given":"Elaine R.","family":"Frawley","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine, University of Washington, Seattle, Washington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joyce E.","family":"Karlinsey","sequence":"additional","affiliation":[{"name":"Department of 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