Helicobacter pylori arginase mutant colonizes arginase Ⅱ knockout mice  

作　　者：Songhee H Kim Melanie L Langford Jean-Luc Boucher Traci L Testerman David J McGee 

机构地区：[1]Department of Microbiology and Immunology,Louisiana State University Health Sciences Center-Shreveport [2]University of Nebraska-Lincoln,School of Biological Sciences,Lincoln [3]Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques,Université Paris Descartes

出　　处：《World Journal of Gastroenterology》2011年第28期3300-3309,共10页世界胃肠病学杂志（英文版）

基　　金：Supported by Public Health Service grant R01-CA101931 (to DJM) from the National Institutes of Health

摘　　要：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.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.

关 键 词：ARGINASE Helicobacter pylori S-（2-boronoethyl）-L-cysteine UREASE Mice 

分 类 号：R57[医药卫生—消化系统]