Helicobacter pylori arginase mutant colonizes arginase Ⅱ knockout mice

• Published in: World journal of gastroenterology : WJG Vol. 17; no. 28; pp. 3300 - 3309
• Main Authors: Kim, Songhee H, Langford, Melanie L, Boucher, Jean-Luc, Testerman, Traci L, McGee, David J
• Format: Journal Article
• Language: English
• Published: United States Baishideng Publishing Group Co., Limited 28.07.2011
• Subjects: Animals; Arginase - antagonists & inhibitors; Arginase - genetics; Arginase - metabolism; Bacterial Proteins - antagonists & inhibitors; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Boronic Acids - metabolism; Helicobacter pylori - enzymology; Helicobacter pylori - genetics; Humans; Mice; Mice, Knockout; Mutation; Original; Rats; Urea - metabolism; Ureohydrolases - metabolism; 基因敲除; 寄生; 小鼠; 尿素酶; 幽门螺杆菌; 突变; 精氨酸酶; 野生型; Arginase; Mice; S-(2-boronoethyl)-L-cysteine; Urease; Helicobacter pylori
• ISSN: 1007-9327; 2219-2840
• DOI: 10.3748/wjg.v17.i28.3300

AIM： To investigate the role of host and bacterial arginases in the colonization of mice by Helicobacter pylori （H.pylori）.METHODS： H.pylori produces a very powerful urease that hydrolyzes urea to carbon dioxide and ammonium,which neutralizes acid.Urease is absolutely essential to H.pylori pathogenesis;therefore,the urea substrate must be in ample supply for urease to work efficiently.The urea substrate is most likely provided by arginase activity,which hydrolyzes L-arginine to L-ornithine and urea.Previous work has demonstrated that H.pylori arginase is surprisingly not required for colonization of wild-type mice.Hence,another in vivo source of the critical urea substrate must exist.We hypothesized that the urea source was provided by host arginase Ⅱ,since this enzyme is expressed in the stomach,and H.pylori has previously been shown to induce the expression of murine gastric arginase Ⅱ.To test this hypothesis,wild-type and arginase （rocF） mutant H.pylori strain SS1 were inoculated into arginase Ⅱ knockout mice.RESULTS： Surprisingly,both the wild-type and rocF mutant bacteria still colonized arginase Ⅱ knockout mice.Moreover,feeding arginase Ⅱ knockout mice the host arginase inhibitor S-（2-boronoethyl）L-cysteine （BEC）,while inhibiting 50% of the host arginase Ⅰ？activity in several tissues,did not block the ability of the rocF mutant H.pylori to colonize.In contrast,BEC poorly inhibited H.pylori arginase activity.CONCLUSION： The in vivo source for the essential urea utilized by H.pylori urease is neither bacterial arginase nor host arginase Ⅱ;instead,either residual host arginase Ⅰ？or agmatinase is probably responsible.