{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T22:56:24Z","timestamp":1774047384879,"version":"3.50.1"},"reference-count":43,"publisher":"Proceedings of the National Academy of Sciences","issue":"24","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2001,11,20]]},"abstract":"<jats:p>The antimicrobial effect of nitric oxide (NO) is an essential part of innate immunity. The vigorous host response to the human gastric pathogen<jats:italic>Helicobacter pylori<\/jats:italic>fails to eradicate the organism, despite up-regulation of inducible NO synthase (iNOS) in the gastric mucosa. Here we report that wild-type strains of<jats:italic>H. pylori<\/jats:italic>inhibit NO production by activated macrophages at physiologic concentrations of<jats:sc>l<\/jats:sc>-arginine, the common substrate for iNOS and arginase. Inactivation of the gene<jats:italic>rocF<\/jats:italic>, encoding constitutively expressed arginase in<jats:italic>H. pylori<\/jats:italic>, restored high-output NO production by macrophages. By using HPLC analysis, we show that<jats:sc>l<\/jats:sc>-arginine is effectively consumed in the culture medium by wild-type but not arginase-deficient<jats:italic>H. pylori<\/jats:italic>. The substantially higher levels of NO generated by macrophages cocultured with<jats:italic>rocF<\/jats:italic>-deficient<jats:italic>H. pylori<\/jats:italic>resulted in efficient killing of the bacteria, whereas wild-type<jats:italic>H. pylori<\/jats:italic>exhibited no loss of survival under these conditions. Killing of the arginase-deficient<jats:italic>H. pylori<\/jats:italic>was NO-dependent, because peritoneal macrophages from iNOS<jats:sup>\u2212\/\u2212<\/jats:sup>mice failed to affect the survival of the<jats:italic>rocF<\/jats:italic>mutant. Thus, bacterial arginase allows<jats:italic>H. pylori<\/jats:italic>to evade the immune response by down-regulating eukaryotic NO production.<\/jats:p>","DOI":"10.1073\/pnas.241443798","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T14:35:07Z","timestamp":1027694107000},"page":"13844-13849","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":314,"title":["<i>Helicobacter pylori<\/i>arginase inhibits nitric oxide production by eukaryotic cells: A strategy for bacterial survival"],"prefix":"10.1073","volume":"98","author":[{"given":"Alain P.","family":"Gobert","sequence":"first","affiliation":[{"name":"Departments of Medicine, Division of Gastroenterology, and Microbiology and Immunology, Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201; Veterans Affairs Maryland Health Care System, Baltimore, MD 21201; and School of Biochemistry and Molecular Genetics, University of New South Wales, Sydney NSW 2052, Australia"}]},{"given":"David J.","family":"McGee","sequence":"additional","affiliation":[{"name":"Departments of Medicine, Division of Gastroenterology, and Microbiology and Immunology, Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201; Veterans Affairs Maryland Health Care System, Baltimore, MD 21201; and School of Biochemistry and Molecular Genetics, University of New South Wales, Sydney NSW 2052, Australia"}]},{"given":"Mahmood","family":"Akhtar","sequence":"additional","affiliation":[{"name":"Departments of Medicine, Division of Gastroenterology, and Microbiology and Immunology, Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201; Veterans Affairs Maryland Health Care System, Baltimore, MD 21201; and School of Biochemistry and Molecular Genetics, University of New South Wales, Sydney NSW 2052, Australia"}]},{"given":"George L.","family":"Mendz","sequence":"additional","affiliation":[{"name":"Departments of Medicine, Division of Gastroenterology, and Microbiology and Immunology, Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201; Veterans Affairs Maryland Health Care System, Baltimore, MD 21201; and School of Biochemistry and Molecular Genetics, University of New South Wales, Sydney NSW 2052, Australia"}]},{"given":"Jamie C.","family":"Newton","sequence":"additional","affiliation":[{"name":"Departments of Medicine, Division of Gastroenterology, and Microbiology and Immunology, Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201; Veterans Affairs Maryland Health Care System, Baltimore, MD 21201; and School of Biochemistry and Molecular Genetics, University of New South Wales, Sydney NSW 2052, Australia"}]},{"given":"Yulan","family":"Cheng","sequence":"additional","affiliation":[{"name":"Departments of Medicine, Division of Gastroenterology, and Microbiology and Immunology, Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201; Veterans Affairs Maryland Health Care System, Baltimore, MD 21201; and School of Biochemistry and Molecular Genetics, University of New South Wales, Sydney NSW 2052, Australia"}]},{"given":"Harry L. T.","family":"Mobley","sequence":"additional","affiliation":[{"name":"Departments of Medicine, Division of Gastroenterology, and Microbiology and Immunology, Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201; Veterans Affairs Maryland Health Care System, Baltimore, MD 21201; and School of Biochemistry and Molecular Genetics, University of New South Wales, Sydney NSW 2052, Australia"}]},{"given":"Keith T.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Departments of Medicine, Division of Gastroenterology, and Microbiology and Immunology, Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD 21201; Veterans Affairs Maryland Health Care System, Baltimore, MD 21201; and School of Biochemistry and Molecular Genetics, University of New South Wales, Sydney NSW 2052, 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