{"id":45011,"date":"2021-08-13T15:28:22","date_gmt":"2021-08-13T07:28:22","guid":{"rendered":"https:\/\/www.gene-optimal.com\/?p=45011"},"modified":"2023-12-05T13:16:54","modified_gmt":"2023-12-05T05:16:54","slug":"mtb-evasion","status":"publish","type":"post","link":"https:\/\/www.gene-optimal.com\/mtb-evasion\/","title":{"rendered":"\u6587\u732e\u5206\u4eab | \u7ed3\u6838\u4e0e\u5bbf\u4e3b\u4e92\u4f5c\u53ca\u514d\u75ab\u9003\u9038\u673a\u5236\u7814\u7a76"},"content":{"rendered":"

\u7ed3\u6838\u5206\u679d\u6746\u83cc\u662f\u4e00\u79cd\u80de\u5185\u75c5\u539f\u83cc\uff0c\u80fd\u591f\u8fd0\u7528\u591a\u79cd\u7b56\u7565\u5e72\u9884\u5bbf\u4e3b\u7ec6\u80de\u7684\u6b63\u5e38\u529f\u80fd\uff0c\u4ece\u800c\u9003\u9038\u5bbf\u4e3b\u514d\u75ab\u53cd\u5e94\uff0c\u8fdb\u800c\u5b9e\u73b0\u5176\u5728\u5bbf\u4e3b\u7ec6\u80de\u4e2d\u7684\u957f\u671f\u5b58\u6d3b\u3002<\/p>\n

\u75c5\u539f\u83cc\u4e0e\u5bbf\u4e3b\u95f4\u76f8\u4e92\u535a\u5f08\u7684\u52a8\u6001\u8fc7\u7a0b\u53ca\u5206\u5b50\u673a\u7406\u4e3a\u6297\u7ed3\u6838\u6cbb\u7597\u3001\u836f\u7269\u7814\u53d1\u7b49\u63d0\u4f9b\u4e86\u65b0\u601d\u8def\u548c\u7279\u5f02\u6027\u9776\u70b9\u3002\u5de8\u566c\u7ec6\u80de\u4e0e\u7ed3\u6838\u5206\u679d\u6746\u83cc\u7684\u76f8\u4e92\u4f5c\u7528\u662f\u7ed3\u6838\u75c5\u53d1\u75c5\u7684\u5173\u952e\u73af\u8282\uff0c\u6291\u5236\u5de8\u566c\u7ec6\u80de\u51cb\u4ea1\u662f\u7ed3\u6838\u5206\u679d\u6746\u83cc\u9003\u9038\u5bbf\u4e3b\u514d\u75ab\u7684\u91cd\u8981\u9014\u7ecf\uff0c\u56e0\u6b64\u7814\u7a76\u7ed3\u6838\u4e0e\u5bbf\u4e3b\u5de8\u566c\u7ec6\u80de\u95f4\u7684\u76f8\u4e92\u4f5c\u7528\u81f3\u5173\u91cd\u8981\u3002<\/p>\n

\u4e0b\u9762\u548c\u5927\u5bb6\u5206\u4eab\u4e00\u7bc7\u7531\u5218\u7fe0\u534e\u3001\u6208\u5b9d\u5b66\u8001\u5e08\u4e3a\u901a\u8baf\u4f5c\u8005\u5728Cellular & Molecular Immunology \u4e0a\u53d1\u8868\u7684\u7efc\u8ff0\u6587\u7ae0\u3002<\/p>\n

\"\"<\/p>\n

\u5728\u8fd9\u7bc7\u7efc\u8ff0\u4e2d\uff0c\u5168\u9762\u3001\u7cfb\u7edf\u5730\u603b\u7ed3\u4e86\u7ed3\u6838\u5206\u679d\u6746\u83cc\u5148\u5929\u514d\u75ab\u9003\u907f\u673a\u5236\uff0c\u4ee5\u4fc3\u8fdb\u5176\u81ea\u8eab\u7684\u7ec6\u80de\u5185\u751f\u5b58\u3002<\/p>\n

\u8be5\u6587\u56de\u987e\u4e86\uff1a<\/p>\n

1\u3001\u7ed3\u6838\u83cc\u8c03\u63a7\u5bbf\u4e3b\u7684\u7ec6\u80de\u5185\u6838\u9178\u53d7\u4f53\u4fe1\u53f7\u901a\u8def\uff1b<\/p>\n

2\u3001\u7ed3\u6838\u5206\u679d\u6746\u83cc\u5982\u4f55\u7ed5\u8fc7\u5bbf\u4e3b\u7ec6\u80de\u56fa\u6709\u514d\u75ab\u7b56\u7565\uff0c\u5982\u819c\u8f6c\u8fd0\u53ca\u819c\u5b8c\u6574\u6027\u3001\u7ec6\u80de\u6b7b\u4ea1\u548c\u81ea\u566c\uff1b<\/p>\n

3\u3001\u7ed3\u6838\u83cc\u64cd\u7eb5\u5bbf\u4e3b\u5148\u5929\u514d\u75ab\u5206\u5b50\u8c03\u8282\u673a\u5236\u7684\u7b56\u7565\uff0c\u5305\u62ec\u6838\u5185\u8c03\u8282\u673a\u5236\u3001\u6cdb\u7d20\u7cfb\u7edf\u548c\u7ec6\u80de\u56fa\u6709\u514d\u75ab\u6210\u5206\u3002\u53ef\u4ee5\u5e2e\u52a9\u6211\u4eec\u66f4\u597d\u5730\u7406\u89e3\u7ed3\u6838\u5206\u679d\u6746\u83cc\u548c\u5bbf\u4e3b\u5148\u5929\u514d\u75ab\u7cfb\u7edf\u4e4b\u95f4\u590d\u6742\u7684\u76f8\u4e92\u4f5c\u7528\uff0c\u4e3a\u4e86\u89e3\u7ed3\u6838\u53d1\u75c5\u673a\u5236\u63d0\u4f9b\u65b0\u7684\u89c1\u89e3\uff0c\u5e76\u6709\u52a9\u4e8e\u75ab\u82d7\u5f00\u53d1\u548c\u7ed3\u6838\u75c5\u6cbb\u7597\u3002<\/p>\n

 <\/p>\n

\u4e00\u3001\u80de\u8d28\u6838\u9178\u611f\u5e94\u9014\u5f84<\/h3>\n

\"\"1-1 \u5bbf\u4e3b\u514d\u75ab\u8bc6\u522b\u7ed3\u6838\u83cc\u7684\u80de\u8d28\u6838\u9178\u611f\u5e94\u9014\u5f84<\/p>\n

 <\/p>\n

\u611f\u67d3\u540e\uff0cMtb \u88ab\u541e\u566c\u7ec6\u80de\u5185\u5316\u4e3a\u541e\u566c\u4f53\uff0c\u5728\u5bbf\u4e3b\u80de\u8d28\u5185\u91ca\u653e\u7ec6\u83cc DNA \u548c RNA\u3002\u80de\u8d28\u4f20\u611f\u5668 cGAS\u3001IFI204\u3001AIM2 \u8bc6\u522b\u7ed3\u6838\u83cc DNA\uff0c\u800c NLRP3\u3001NOD2\u3001RIG-I\u3001MDA5\u3001PKR \u8bc6\u522bRNA\u3002\u6d3b\u5316\u7684\u80de\u8d28 DNA\/RNA \u4f20\u611f\u5668\u8fdb\u4e00\u6b65\u8bf1\u5bfc\u708e\u75c7\u5c0f\u4f53\u6216 NF-\u03baB \u548c IRF3 \u4ecb\u5bfc\u7684\u5148\u5929\u514d\u75ab\u901a\u8def\u7684\u6fc0\u6d3b\uff0c\u4ee5\u8c03\u8282\u5bbf\u4e3b\u6297\u7ed3\u6838\u83cc\u53cd\u5e94\u3002<\/p>\n

 <\/p>\n

\u4e8c\u3001\u5bbf\u4e3b\u56fa\u6709\u514d\u75ab\u7b56\u7565<\/h3>\n

\u7ed3\u6838\u83cc\u6fc0\u6d3b\u5bbf\u4e3b\u7ec6\u80de\u514d\u75ab\u9014\u5f84\uff0c\u5bfc\u81f4\u4e00\u7cfb\u5217\u7684\u6297\u83cc\u4f5c\u7528\uff0c\u5982\u7ec6\u80de\u541e\u566c\u3001\u51cb\u4ea1\u7b49\uff0c\u7136\u800c\u8fd9\u4e9b\u4f5c\u7528\u53ef\u4ee5\u88ab Mtb \u9632\u5fa1\u548c\u8c03\u8282\uff0c\u4f7f\u5f97\u81ea\u8eab\u5728\u7ec6\u80de\u4e2d\u957f\u671f\u751f\u5b58\u3002<\/p>\n

Mtb \u7684\u8c03\u63a7\u7b56\u7565\uff1a<\/strong>\u5e72\u9884\u5bbf\u4e3b\u7ec6\u80de\u819c\u8f6c\u8fd0\u53ca\u819c\u5b8c\u6574\u6027\u3001\u7ec6\u80de\u6b7b\u4ea1\u3001\u81ea\u566c\u8fc7\u7a0b\uff0c\u5982\u56fe1-2\u6240\u793a\uff1a<\/p>\n

\"\"1-2 Mtb\u611f\u67d3\u671f\u95f4\u5bbf\u4e3b\u7ec6\u80de\u7684\u514d\u75ab\u53cd\u5e94<\/p>\n

 <\/p>\n

a\u3001Mtb \u8c03\u8282\u7ec6\u80de\u819c\u8f6c\u8fd0\u53ca\u819c\u5b8c\u6574\u6027\uff1a<\/strong>(1)\u7ed3\u6838\u83cc\u4fc3\u8fdbRab5+\u3001Rab11+\u800c\u6291\u5236 Rab7+\u3001Rab20+\u7684\u6838\u5185\u4f53\u52df\u96c6\u5230\u541e\u566c\u5c0f\u4f53\u3002(2)\u6291\u5236\u6eb6\u9176\u4f53\u878d\u5408\uff0c\u5f15\u8d77\u541e\u566c\u4f53\u635f\u4f24\uff0c\u4f7f\u5176\u9003\u9038\u5230\u5bbf\u4e3b\u7ec6\u80de\u8d28\u3002(3)\u7ed3\u6838\u83cc\u8bf1\u5bfc\u7ebf\u7c92\u4f53\u819c\u901a\u900f\u6027\u8f6c\u53d8 (MPT)\uff0c\u6291\u5236\u5bbf\u4e3b\u7ec6\u80de\u819c\u4fee\u590d\uff0c\u8c03\u8282 ejectosome \u5f62\u6210\u548c\u5916\u6ccc\u4f53\u8fd0\u8f93\u3002<\/p>\n

b\u3001\u7ec6\u80de\u6b7b\u4ea1\uff1a<\/strong>\u5728 Mtb \u611f\u67d3\u8fc7\u7a0b\u4e2d\uff0c\u53ef\u80fd\u4f1a\u8bf1\u5bfc\u7ec6\u80de\u6b7b\u4ea1\u6a21\u5f0f\uff0c\u5176\u4e2d\u51cb\u4ea1\u548c\u7126\u4ea1\u88ab\u8ba4\u4e3a\u53ef\u6291\u5236\u7ec6\u83cc\u80de\u5185\u751f\u957f\uff0c\u4fc3\u8fdb\u6297\u7ed3\u6838\u514d\u75ab\u53cd\u5e94\uff0c\u800c\u574f\u6b7b\u6027\u51cb\u4ea1\u548c\u94c1\u6b7b\u4ea1\u5219\u6709\u5229\u4e8e\u7ed3\u6838\u5206\u679d\u6746\u83cc\u7684\u590d\u5236\u548c\u4f20\u64ad\u3002\u6b64\u5916\uff0c\u4e2d\u6027\u7c92\u7ec6\u80de\u80de\u5916\u8bf1\u6355 (NET) \u76f8\u5173 NETosis \u53ef\u80fd\u8bf1\u6355\u7ed3\u6838\u6746\u83cc\uff0c\u5e76\u4fc3\u8fdb\u514d\u75ab\u7ec6\u80de\u76f8\u4e92\u4f5c\u7528\u3002<\/p>\n

c\u3001\u7ec6\u80de\u81ea\u566c\uff1a<\/strong>xenophagy \u548c LAP \u9014\u5f84\u90fd\u6709\u52a9\u4e8e\u5bbf\u4e3b\u81ea\u566c\u76f8\u5173\u7684\u514d\u75ab\u6e05\u9664\u3002xenophagy \u9014\u5f84\u53ef\u901a\u8fc7\u7ed3\u6838\u83cc\u548c Mtb \u541e\u566c\u4f53\u7684 E3 \u6cdb\u7d20\u8fde\u63a5\u9176\uff08Parkin \u548c smurf1\uff09\u6cdb\u7d20\u5316\u6216\u901a\u8fc7 Mtb \u8868\u9762\u86cb\u767d Rv1468c \u7684\u7ed3\u5408\uff1bLAP \u9014\u5f84\u7531 NOX2 \u548c RUBCN \u4ecb\u5bfc\uff0c\u4fc3\u8fdb LC3 \u5728 Mtb \u541e\u566c\u4f53\u4e0a\u7684\u52df\u96c6\u3002\u7136\u800c\uff0cMtb \u53ef\u4ee5\u901a\u8fc7\u8c03\u8282\u5bbf\u4e3bmiRNA\u6216\u4f7f\u7528\u4e00\u7cfb\u5217\u7684\u86cb\u767d\u6548\u5e94\u5b50 (\u5982 ESX-1\u3001SapM\u3001EIS \u548c CpsA) \u6765\u7834\u574f xenophagy \u548c LAP \u9014\u5f84\u3002<\/p>\n

 <\/p>\n

\u4e09\u3001\u7ed3\u6838\u83cc\u8c03\u8282\u5bbf\u4e3b\u5148\u5929\u514d\u75ab\u673a\u5236<\/h3>\n

Mtb \u901a\u8fc7\u5bbf\u4e3b-\u75c5\u539f\u4f53\u5206\u5b50\u76f8\u4e92\u4f5c\u7528\u6765\u64cd\u7eb5\u5bbf\u4e3b\u7ec6\u80de\u56fa\u6709\u514d\u75ab\u5e94\u7b54\u7684\u8c03\u63a7\u673a\u5236\uff0c\u5982\u56fe1-3\u6240\u793a\uff1a<\/p>\n

\"\"1-3 Mtb\u6548\u5e94\u5206\u5b50\u9776\u6807\u5bbf\u4e3b\u7ec6\u80de\u548c\u56fa\u6709\u514d\u75ab\u7684\u5206\u5b50\u8c03\u63a7\u673a\u5236<\/p>\n

 <\/p>\n

\u5728\u611f\u67d3\u540e\uff0cMtb \u5c06\u591a\u79cd\u6548\u5e94\u86cb\u767d\u4f20\u9012\u5230\u5bbf\u4e3b\u7ec6\u80de\u4e2d\uff0c\u4e0e\u5bbf\u4e3b\u6cdb\u7d20\u7cfb\u7edf\u7684\u5206\u5b50\u7ec4\u5206\u548c\u5176\u5b83\u56fa\u6709\u7ec6\u80de\u514d\u75ab\u86cb\u767d\u76f4\u63a5\u76f8\u4e92\u4f5c\u7528\uff0c\u4ece\u800c\u7834\u574f\u5bbf\u4e3b\u56fa\u6709\u514d\u75ab\u3002\u540c\u65f6\uff0c\u4e00\u4e9b Mtb \u6548\u5e94\u86cb\u767d\u88ab\u786e\u5b9a\u4e3a\u6838\u8c03\u8282\u7d20\uff0c\u5b83\u4eec\u8fdb\u5165\u5bbf\u4e3b\u7ec6\u80de\u6838\uff0c\u53c2\u4e0e\u5bbf\u4e3b\u5148\u5929\u514d\u75ab\u5e94\u7b54\u7684\u8868\u89c2\u9057\u4f20\u548c\u8f6c\u5f55\u8c03\u63a7\u3002<\/p>\n

1\u3001Mtb\u9776\u5411\u6838\u5185\u514d\u75ab\u8c03\u8282\u673a\u5236\uff1a<\/strong><\/p>\n

\uff081\uff09\u4e00\u4e9bMtb\u6838\u8c03\u8282\u7d20\u4f5c\u4e3a\u7ec4\u86cb\u767d\u4fee\u9970\u9176\u53c2\u4e0e\u5bbf\u4e3b\u514d\u75ab\u53cd\u5e94\u7684\u8868\u89c2\u9057\u4f20\u8c03\u63a7\u3002\u76ee\u524d\uff0c\u5df2\u786e\u5b9a\u7684\u9776\u5411\u548c\u4fee\u9970\u5bbf\u4e3b\u7ec4\u86cb\u767d\u7684 Mtb\u6548\u5e94\u56e0\u5b50\u6709 EIS\u3001Rv1988\u3001Rv3423.1\u3002<\/p>\n

\n
    \n
  1. \u611f\u67d3\u8fc7\u7a0b\u4e2d\uff0cEIS \u589e\u52a0\u7ec4\u86cb\u767d H3 \u7684\u4e59\u9170\u5316\u6c34\u5e73\u4ee5\u8c03\u8282\u5bbf\u4e3b\u81ea\u566c\u6fc0\u6d3b\u3002<\/li>\n
  2. Rv1988 \u5b9a\u4f4d\u4e8e\u5bbf\u4e3b\u67d3\u8272\u8d28\uff0c\u4f5c\u4e3a\u4e00\u79cd\u529f\u80fd\u6027\u7684\u7532\u57fa\u8f6c\u79fb\u9176\uff0c\u53ef\u5bf9 H3R42 \u4e0a\u7684\u7cbe\u6c28\u9178\u6b8b\u57fa\u8fdb\u884c\u4e8c\u7532\u57fa\u5316\uff0c\u4ee5\u6291\u5236\u4e00\u7cfb\u5217\u53c2\u4e0e\u6d3b\u6027\u6c27 (ROS) \u4ea7\u751f\u7684\u5bbf\u4e3b\u57fa\u56e0\u3002<\/li>\n
  3. Rv3423.1 \u8868\u73b0\u51fa\u7ec4\u86cb\u767d\u4e59\u9170\u8f6c\u79fb\u9176\u6d3b\u6027\uff0c\u5e76\u9776\u5411\u5bbf\u4e3b H3K9 \u548c H3K14\u3002<\/li>\n<\/ol>\n<\/section>\n

    \uff082\uff09\u5176\u5b83 Mtb \u6838\u8c03\u8282\u7d20<\/p>\n

    \n
      \n
    1. Rv2966c \u662f\u4e00\u79cd5-\u7532\u57fa\u80de\u5627\u5576\u7279\u5f02\u6027 DNA \u7532\u57fa\u8f6c\u79fb\u9176\uff0c\u4e3b\u8981\u53c2\u4e0e\u5bbf\u4e3b\u57fa\u56e0\u7ec4 DNA \u7684\u7532\u57fa\u5316\uff0c\u4e3b\u8981\u662f\u611f\u67d3\u975e CpG \u80de\u5627\u5576\u3002<\/li>\n
    2. \u4e00\u4e9b Mtb \u86cb\u767d\u6548\u5e94\u7269\u8868\u73b0\u51fa\u53cc\u91cd\u8c03\u63a7\u529f\u80fd\uff0c\u4e0d\u4ec5\u9488\u5bf9\u5bbf\u4e3b\u7684\u80de\u8d28\u6210\u5206\uff0c\u800c\u4e14\u6a21\u4eff\u53c2\u4e0e\u5bbf\u4e3b\u6838\u5185\u8fc7\u7a0b\u7684\u771f\u6838\u8f6c\u5f55\u56e0\u5b50\u3002\u2460 \u5206\u6ccc\u86cb\u767d PPE2 \u901a\u8fc7 SH3 \u6837\u7ed3\u6784\u57df\u76f4\u63a5\u4e0e\u5bbf\u4e3b NADPH \u6c27\u5316\u9176\u7684\u80de\u8d28\u4e9a\u57fa p67phox\u00a0<\/sup>\u76f8\u4e92\u4f5c\u7528\uff1bPPE2 \u8fd8\u53ef\u4ee5\u4e0e NOS2 \u542f\u52a8\u5b50\u7ed3\u5408\uff0c\u9650\u5236\u5bbf\u4e3b ROS \u7684\u4ea7\u751f\u3002\u2461 PtpA \u88ab\u9001\u5165\u5bbf\u4e3b\u7ec6\u80de\u8d28\uff0c\u6291\u5236\u5bbf\u4e3b\u708e\u75c7\u514d\u75ab\u53cd\u5e94\uff0c\u4e5f\u53ef\u4ee5\u8fdb\u5165\u611f\u67d3\u7ec6\u80de\u7684\u7ec6\u80de\u6838\uff0c\u4e0e\u591a\u79cd\u5bbf\u4e3b\u57fa\u56e0\uff08\u5982 GADD45A\uff09\u7ed3\u5408\u5e76\u8c03\u8282\u5176\u8868\u8fbe\uff0c\u4ece\u800c\u5f71\u54cd\u7ec6\u80de\u7684\u589e\u6b96\u548c\u8fc1\u79fb\u3002<\/li>\n<\/ol>\n<\/section>\n

      2\u3001Mtb \u9776\u70b9\uff1a\u5bbf\u4e3b\u6cdb\u7d20\u7cfb\u7edf<\/strong><\/p>\n

      \uff081\uff09Mtb\u6cdb\u7d20\u7ed3\u5408\u86cb\u767d Rv1468c \u4f4d\u4e8e\u7ec6\u83cc\u8868\u9762\uff0c\u5b83\u76f4\u63a5\u62db\u52df\u5bbf\u4e3b\u80de\u8d28\u6cdb\u7d20\uff0c\u89e6\u53d1 xenophagy\uff0c\u9650\u5236\u5bbf\u4e3b\u708e\u75c7\u53cd\u5e94\u3002<\/p>\n

      \uff082\uff09Mtb PtpA \u901a\u8fc7\u4e00\u4e2a\u72ec\u7279\u7684\u6cdb\u7d20\u4e92\u4f5c\u57fa\u5143\u6837\u533a\u57df\u4e0e\u6cdb\u7d20\u76f4\u63a5\u76f8\u4e92\u4f5c\u7528\uff0c\u6fc0\u6d3b\u5bbf\u4e3b p-JNK\u3001p-p38 \u548c p-VPS33B \u53bb\u78f7\u9178\u5316\uff0c\u4ece\u800c\u6291\u5236\u5148\u5929\u514d\u75ab\u5e94\u7b54\u3002<\/p>\n

      \uff083\uff09PtpA \u4e0e\u5bbf\u4e3b E3 \u6cdb\u7d20\u8fde\u63a5\u9176\uff08\u5305\u542bTRIM27\u7684\u4e09\u90e8\u5206\u57fa\u5143\uff09\u7684RING\u7ed3\u6784\u57df\u7ed3\u5408\uff0c\u4ee5\u5bf9\u6297TRIM27\u4fc3\u8fdb\u7684\u708e\u75c7\u514d\u75ab\u53cd\u5e94\u548c\u7ec6\u80de\u51cb\u4ea1\u3002<\/p>\n

      \uff084\uff09Mtb \u5206\u6ccc\u86cb\u767d Rv0222\uff0c\u4e0e\u5bbf\u4e3b E3 \u6cdb\u7d20\u8fde\u63a5\u9176 ANAPC2\u7ed3\u5408\uff0c\u4ecb\u5bfc Rv0222 \u7684 k11 \u8fde\u63a5\u6cdb\u7d20\u5316\uff0c\u4ece\u800c\u6291\u5236\u5bbf\u4e3b NF-\u03baB \u6fc0\u6d3b\u3002<\/p>\n

      \uff085\uff09Mtb \u5206\u6ccc\u7684\u6bd2\u529b\u56e0\u5b50 LpqN \u4e0e E3 \u6cdb\u7d20\u8fde\u63a5\u9176 CBL \u76f8\u4e92\u4f5c\u7528\uff0cCBL \u5728\u7ec6\u80de\u5bf9\u611f\u67d3\u7684\u5185\u5728\u53cd\u5e94\u4e2d\u53d1\u6325\u8c03\u8282\u4f5c\u7528\u3002<\/p>\n

      \uff086\uff09Mtb \u5206\u6ccc\u7684\u6bd2\u529b\u56e0\u5b50 Rv3354 \u80fd\u591f\u4e0e CSN5 \u76f8\u4e92\u4f5c\u7528\uff0c\u5bfc\u81f4 cullin-RING \u4e0d\u7a33\u5b9a\u3002<\/p>\n

      \u8d8a\u6765\u8d8a\u591a\u7684\u8bc1\u636e\u8868\u660e\uff0c\u6cdb\u7d20\u7cfb\u7edf\u7ecf\u5e38\u88ab\u5165\u4fb5\u7684\u75c5\u539f\u4f53\u5438\u6536\uff0c\u7136\u540e\u5728\u5bbf\u4e3b\u7684\u514d\u75ab\u53cd\u5e94\u4e2d\u8d77\u7740\u6539\u53d8\u8c03\u8282\u7684\u4f5c\u7528\u3002<\/p>\n

      3\u3001\u7ed3\u6838\u5206\u679d\u6746\u83cc\u4ee5\u56fa\u6709\u7684\u7ec6\u80de\u514d\u75ab\u6210\u5206\u4e3a\u9776\u70b9\uff1a<\/strong><\/p>\n

      \uff081\uff09EIS \u9776\u5411\u5e76\u4e59\u9170\u5316\u4e1d\u88c2\u539f\u6d3b\u5316\u7684\u86cb\u767d\u6fc0\u9176\u78f7\u9178\u9176-7\uff08MKP-7\uff09\u6765\u963b\u6b62\u5bbf\u4e3b JNK \u4f9d\u8d56\u7684\u514d\u75ab\u5e94\u7b54\u3002<\/p>\n

      \uff082\uff09MPT53 \u53ef\u4ee5\u76f4\u63a5\u6c27\u5316 TAK1 \u4e0a\u7684\u786b\u9187\uff0c\u4ee5\u4fc3\u8fdb TAK1 \u4ecb\u5bfc\u7684\u5bbf\u4e3b\u8d85\u708e\u75c7\u514d\u75ab\u53cd\u5e94\u3002<\/p>\n

      \uff083\uff09\u5206\u6ccc\u86cb\u767dPPE2\u901a\u8fc7SH3\u6837\u7ed3\u6784\u57df\u76f4\u63a5\u4e0e\u5bbf\u4e3b NADPH \u6c27\u5316\u9176\u7684\u80de\u8d28\u4e9a\u57fa p67phox\u00a0<\/sup>\u76f8\u4e92\u4f5c\u7528\uff0c\u6291\u5236 ROS \u7684\u4ea7\u751f\uff0c\u6709\u5229\u4e8e Mtb \u5728\u5de8\u566c\u7ec6\u80de\u5185\u7684\u5b58\u6d3b\u3002<\/p>\n

       <\/p>\n

      \n

       <\/p>\n

      \u63a5\u4e0b\u6765\u548c\u5927\u5bb6\u5206\u4eab\u5218\u7fe0\u534e\u6559\u6388\u56e2\u961f\u7684\u4e00\u7bc7\u7814\u7a76\u8bba\u6587\uff0c\u662f\u4e0e\u5317\u4eac\u5e08\u8303\u5927\u5b66\u90b1\u5c0f\u6ce2\u6559\u6388\u56e2\u961f\u4ee5\u53ca\u5fae\u751f\u7269\u7814\u7a76\u6240\u9ad8\u798f\u9662\u58eb\u56e2\u961f\u6700\u65b0\u5408\u4f5c\u53d1\u8868\u5728 EMBO reports \u4e0a\u7684\u9898\u4e3a\u201cMycobacterium tuberculosis<\/em>\u00a0protein kinase G acts as an unusual ubiquitinating enzyme to impair host immunity\u201d\u4e00\u6587\u3002<\/p>\n

      \"\"<\/p>\n

      \u8be5\u6587\u63ed\u793a\u4e86 Mtb PknG \u53ef\u4e0e\u5bbf\u4e3b\u6cdb\u7d20\u7cfb\u7edf\u7684\u53e6\u4e00\u79cd\u5173\u952e\u86cb\u767d\u2014\u2014\u6cdb\u7d20\u8026\u5408\u9176\uff08E2\uff09UbcH7 \u53d1\u751f\u7279\u5f02\u6027\u7ed3\u5408\uff0c\u5e76\u50ac\u5316\u4e00\u79cd\u975e\u7ecf\u5178\u7684\u4e24\u6b65\u6cdb\u7d20\u5316\u7ea7\u8054\u53cd\u5e94\u6765\u9776\u5411\u8c03\u63a7\u5bbf\u4e3b\u6cdb\u7d20\u7cfb\u7edf\uff0c\u8fdb\u800c\u6291\u5236\u5bbf\u4e3b\u7684\u56fa\u6709\u514d\u75ab\u5e94\u7b54\u3002<\/p>\n

      \u7814\u7a76\u53d1\u73b0 Mtb PknG \u662f\u5177\u6709\u975e\u7ecf\u5178\u7684\u6cdb\u7d20\u6fc0\u6d3b\u9176\uff08E1\uff09\u548c\u6cdb\u7d20\u8fde\u63a5\u9176\uff08E3\uff09\u6d3b\u6027\u7684\u6548\u5e94\u86cb\u767d\uff08\u4e14\u63ed\u793a\u4e86 PknG \u53ef\u901a\u8fc7\u4e24\u6b65\u4ecb\u5bfc\u5e95\u7269\u7684\u6cdb\u7d20\u5316\u4fee\u9970\uff09\uff0c\u5e76\u53ef\u5229\u7528\u5176\u53cc\u529f\u80fd\u9176\u6d3b\u6027\u4fc3\u8fdb\u5bbf\u4e3b\u7ec6\u80de\u4e2d\u7684 TRAF2 \u548c TAK1 \u7684\u6cdb\u7d20\u5316\u53ca\u964d\u89e3\uff0c\u6700\u7ec8\u6291\u5236 NF-\u03baB \u56fa\u6709\u514d\u75ab\u4fe1\u53f7\u901a\u8def\u7684\u6d3b\u5316\uff0c\u4ece\u800c\u4fc3\u8fdb\u75c5\u539f\u4f53\u5728\u7ec6\u80de\u5185\u751f\u5b58\u3002<\/p>\n

       <\/p>\n

      \u4e00\u3001Mtb PknG\u4e0eE2\u86cb\u767dUbcH7\u4e92\u4f5c<\/h3>\n

      \u672c\u7814\u7a76\u901a\u8fc7\u9175\u6bcd\u53cc\u6742\u4ea4\u65b9\u6cd5\u3001\u514d\u75ab\u6c89\u6dc0\u3001pull down \u7b49\u5b9e\u9a8c\uff0c\u8bc1\u660e E2 \u86cb\u767d UbcH7 \u4e0e pknG \u86cb\u767d\u4e92\u4f5c\u3002<\/p>\n

      \"\"\u56fe2-1 Mtb PknG\u901a\u8fc7Ubl\u7ed3\u6784\u57df\u4e0eE2\u86cb\u767dUbcH7\u76f8\u4e92\u4f5c\u7528\u3002<\/p>\n

      <\/section>\n
      \u672c\u5b9e\u9a8c\u4e2d\u6784\u5efa\u4e86\u7cfb\u5217 PknG \u7a81\u53d8\u4f53\uff1aMtb \u2206pknG\uff08PknG \u57fa\u56e0\u6572\u9664\u83cc\u682a\uff09\u3001\u2206pknG:PknG \u2206UbI\uff08PknG UbI \u533a\u57df\u7f3a\u5931\u83cc\u682a\uff09\u3001\u2206pknG:PknG E190A\uff08PknG Glu190Ala \u70b9\u7a81\u53d8\u83cc\u682a\uff09\u3002\u5de8\u566c\u7ec6\u80de\u5206\u522b\u4e0e WT Mtb \u53ca\u7a81\u53d8\u4f53\u83cc\u682a\u8fdb\u884c\u514d\u75ab\u5171\u6c89\u6dc0\uff08\u56fe2-1\uff09\uff0c\u53d1\u73b0\u7a81\u53d8\u4f53\u83cc\u682a\u7684 PknG \u4e0e UbcH7 \u7684\u76f8\u4e92\u4f5c\u7528\u6d88\u5931\uff0cE190A \u4e0d\u5f71\u54cd\u6fc0\u9176\u6d3b\u6027\uff0c\u4f46\u4f1a\u5f71\u54cd PknG \u4e0e UbcH7 \u4e92\u4f5c\uff0c\u7ed3\u679c\u8868\u660e\uff0c\u5728\u5206\u679d\u6746\u83cc\u611f\u67d3\u8fc7\u7a0b\u4e2d\uff0cMtb PknG \u901a\u8fc7\u4e00\u4e2aUbl \u7ed3\u6784\u57df\u4e0e\u5bbf\u4e3b E2 \u86cb\u767d UbcH7 \u76f8\u4e92\u4f5c\u7528\u3002<\/section>\n
      \n

      <\/h3>\n

      \u4e8c\u3001PknG\u5177\u6709\u975e\u7ecf\u5178E1\u5f02\u80bd\u9176\u6d3b\u6027<\/h3>\n

      \u4f53\u5916\u6cdb\u7d20\u5076\u8054\u5b9e\u9a8c\uff0c\u53d1\u73b0 PknG \u53ef\u4ee5\u4f5c\u4e3a\u4e00\u79cd\u975e\u7ecf\u5178\u7684 E1\uff0c\u5229\u7528 ATP \u4f5c\u4e3a\u80fd\u91cf\u6765\u6e90\uff0c\u4fc3\u8fdb Ub \u5728 UbcH7 \u4e0a\u7684\u7ed3\u5408\u3002\u5bf9PknG \u50ac\u5316\u7684 UbcH7 \u5076\u8054\u7684\u65f6\u95f4\u8fc7\u7a0b\u5206\u6790\u8fdb\u4e00\u6b65\u53d1\u73b0\uff0c\u572830\u5206\u949f\u5185\uff0cUbcH7 \u5076\u8054\u7684\u6c34\u5e73\u968f\u7740\u65f6\u95f4\u7684\u63a8\u79fb\u800c\u589e\u52a0\uff08\u56fe2-2\uff09\u3002<\/p>\n

      \"\"\u56fe2-2 \u4f53\u5916\u6cdb\u7d20\u5076\u8054\u5b9e\u9a8c<\/p>\n

      \u4e0e\u4f20\u7edf\u7684 E1 \u4e0d\u540c\uff0cPknG \u53ef\u4ee5\u76f4\u63a5\u50ac\u5316 Ub \u5076\u8054\u5230 UbcH7 \u4e0a\uff0c\u7ed5\u8fc7 PknG-Ub \u952e\u5408\u6b65\u9aa4\uff08\u56fe2-3\uff09\u3002<\/p>\n

      \"\"\u56fe2-3 Mtb PknG\u4f53\u5916\u50ac\u5316Ub\u4e0eUbcH7\u7ed3\u5408
      \n\u6ce8\uff1aPknG K181M\uff0c\u65e0\u6d3b\u6027\u6fc0\u9176\u7a81\u53d8\u3002<\/p>\n

       <\/p>\n

      Lys82 \u4e3a PknG \u50ac\u5316 Ub \u7ed3\u5408\u81f3 UbcH7 \u7684\u4f4d\u70b9\uff0c\u5176\u95f4\u65e0\u9700\u5f62\u6210\u786b\u916f\u952e\u8fde\u63a5\u7684 PknG-Ub \u4e2d\u95f4\u4f53\uff0c\u800c\u7ecf\u5178\u7684 E1 \u901a\u5e38\u50ac\u5316 Ub \u4ee5\u786b\u916f\u952e\u7684\u5f62\u5f0f\u7ed3\u5408\u81f3 UbcH7 \u7684 Cys86 \u4f4d\u70b9\uff0c\u4e14\u5176\u95f4\u9700\u8981\u5f62\u6210\u786b\u916f\u952e\u8fde\u63a5\u7684 E1-Ub \u4e2d\u95f4\u4f53\uff08\u56fe2-4A\uff09\u3002<\/p>\n

      \"\"\u56fe2-4 Mtb PknG\u662f\u5177\u6709\u5f02\u80bd\u9176\u6d3b\u6027\u7684\u975e\u7ecf\u5178E1\u9176\u6d3b<\/p>\n

       <\/p>\n

      PknG \u5177\u6709 Ubl \u7ed3\u6784\u57df\u4f9d\u8d56\u7684\u975e\u7ecf\u5178 E1 \u6d3b\u6027\uff0c\u53ef\u4ee5\u5728 ATP \u5b58\u5728\u4e0b\u76f4\u63a5\u50ac\u5316 Ub \u5076\u8054\u5230 UbcH7 \u7684 Lys82 \u4e0a\uff0c\u4ece\u800c\u53d6\u6d88 UbcH7 \u7684\u5178\u578b E2 \u6d3b\u6027\u3002\u8fdb\u4e00\u6b65\u5b9e\u9a8c\u8868\u660e\uff0c PknG \u5177\u6709\u4f9d\u8d56\u4e8e Ile87 \u6b8b\u57fa\u7684\u5f02\u80bd\u9176\u6d3b\u6027\uff08\u50ac\u5316 Ub \u81ea UbcH7-Ub \u590d\u5408\u7269\u4e0a\u89e3\u79bb\uff09\uff08\u56fe2-4B\u3001C\uff09\u3002<\/p>\n

       <\/p>\n

      \u4e09\u3001Mtb PknG\u901a\u8fc7\u6291\u5236NF-\u03baB\u6fc0\u6d3b\u6765\u6291\u5236\u5bbf\u4e3b\u5148\u5929\u514d\u75ab<\/h3>\n

      Mtb PknG \u662f\u5426\u8c03\u8282\u5bbf\u4e3b\u56fa\u6709\u514d\u75ab\u4fe1\u53f7\u901a\u8def\uff0c\u5728 HEK293T \u7ec6\u80de\u4e2d\u5bf9 PknG \u53ca\u5176\u7a81\u53d8\u57fa\u56e0\u8fdb\u884c\u8367\u5149\u7d20\u9176\u62a5\u544a\u5b9e\u9a8c\uff0cPknG \u53ef\u663e\u8457\u6291\u5236 TNFa \u8bf1\u5bfc\u7684 NF-\u03baB \u4fe1\u53f7\u901a\u8def\uff0cE190A \u7a81\u53d8\u6d88\u9664\u4e86 PknG \u4ecb\u5bfc\u7684 NF-\u03baB \u6fc0\u6d3b\u7684\u6291\u5236\uff08\u7834\u574f PknG \u548c UbcH7 \u4e4b\u95f4\u7684\u76f8\u4e92\u4f5c\u7528\uff09\uff0c\u800c\u5176\u5b83 PknG \u7a81\u53d8\uff08K181M\u3001PknG \u2206TPR\uff09\uff0c\u6ca1\u6709\u5f15\u8d77\u8fd9\u79cd\u5f71\u54cd\uff08\u56fe2-5 A)\u3002<\/p>\n

      \"\"\u56fe2-5 Mtb PknG\u4ee5E190\u4f4d\u70b9\u4f9d\u8d56\u7684\u65b9\u5f0f\u6291\u5236NF-\u03baB\u7684\u6fc0\u6d3b<\/p>\n

       <\/p>\n

      \u6784\u5efa\u6572\u9664\u83cc\u682a Mtb \u2206pknG\u3001\u56de\u8865\u83cc\u682a\uff0c\u901a\u8fc7 qPCR\u3001ELISA \u68c0\u6d4b\u7ed3\u6838\u611f\u67d3\u5de8\u566c\u7ec6\u80de\u8fc7\u7a0b\u4e2d\u7ec6\u80de\u56e0\u5b50\u7684\u8868\u8fbe\u662f\u5426\u53d7 Mtb PknG \u6216\u5176\u7a81\u53d8\u4f53\u7684\u8c03\u63a7\u3002<\/p>\n

      PknG \u7684\u7f3a\u5931\u4fc3\u8fdb\u4e86 TNF \u548c IL-6 \u7b49\u708e\u75c7\u56e0\u5b50\u7684\u4ea7\u751f\uff08\u56fe2-5B\u3001C\uff09\uff0c\u964d\u4f4e\u4e86\u5de8\u566c\u7ec6\u80de\u4e2d\u7684\u7ec6\u83cc\u5b58\u6d3b\u7387\uff08\u56fe2-5D\uff09\uff0c\u8fd9\u8868\u660e PknG \u6291\u5236\u4e86\u708e\u75c7\u56e0\u5b50\u7684\u4ea7\u751f\uff0c\u63d0\u9ad8\u4e86\u7ec6\u83cc\u7684\u7ec6\u80de\u5185\u751f\u5b58\u3002<\/p>\n

      E190A \u7a81\u53d8\u57fa\u672c\u6d88\u9664\u4e86 PknG \u4ecb\u5bfc\u7684\u5bf9\u5de8\u566c\u7ec6\u80de\u4e2d\u7ec6\u80de\u56e0\u5b50\u4ea7\u751f\u7684\u6291\u5236\u4f5c\u7528\uff08\u7279\u522b\u662f\u5728\u611f\u67d3\u540e0-8 h\uff09\uff0c\u800c K181M \u7a81\u53d8\u90e8\u5206\u6d88\u9664\u4e86 Mtb PknG \u4ecb\u5bfc\u7684\u5bf9\u5de8\u566c\u7ec6\u80de\u4e2d\u7ec6\u83cc\u5b58\u6d3b\u7684\u6291\u5236\u4f5c\u7528\uff08\u7279\u522b\u662f\u5728\u611f\u67d3\u540e8 h\uff09\u3002<\/p>\n

      PknG E190A \u548c K181M \u53cc\u7a81\u53d8 Mtb \u83cc\u682a (DpknG:PknG K181M,E190A) \u6bd4 DpknG:PknG K181M \u548c DpknG:PknG E190A \u83cc\u682a\u8868\u73b0\u51fa\u66f4\u9ad8\u7684\u7ec6\u80de\u56e0\u5b50\u4ea7\u91cf\u548c\u66f4\u4f4e\u7684\u7ec6\u83cc\u8d1f\u8377\uff0c\u7279\u522b\u662f\u5728\u611f\u67d3\u540e8-24 h\uff08\u56fe2-5 B-D)\u3002<\/p>\n

      \u4ee5\u4e0a\u7ed3\u679c\u8868\u660e\uff0cMtb PknG \u80fd\u591f\u4ee5\u4f9d\u8d56\u4e8e\u5176 Ubl \u7ed3\u6784\u57df\u7684\u65b9\u5f0f\u7279\u5f02\u6027\u6291\u5236 NF-\u03baB \u6fc0\u6d3b\u3002<\/p>\n

       <\/p>\n

      \u56db\u3001Mtb PknG\u5177\u6709\u975e\u7ecf\u5178E1\u548cE3\u6d3b\u6027\uff0c\u4fc3\u8fdbTRAF2\u548cTAK1\u7684\u964d\u89e3<\/h3>\n

      \u5728 HEK293T \u7ec6\u80de\u4e2d\u5bf9 PknG \u8fdb\u884c\u8367\u5149\u7d20\u9176\u62a5\u544a\u5b9e\u9a8c\uff0c\u7ed3\u679c\u8868\u660e\uff0cPknG \u6291\u5236\u4e86 TAK1 \u6216 TAB1 \u4ecb\u5bfc\u7684 NF-\u03baB \u6fc0\u6d3b(\u56fe2-6 A)\u3002\u8f6c\u67d3 HEK293T \u7ec6\u80de\u548c\u611f\u67d3\u5de8\u566c\u7ec6\u80de\u7684\u514d\u75ab\u5171\u6c89\u6dc0\u5206\u6790\u8fdb\u4e00\u6b65\u8bc1\u660e PknG \u4e0e TRAF2 \u548c TAK1 \u76f8\u4e92\u4f5c\u7528\uff08\u56fe2-6 B-C\uff09\u3002\u5728 WT Mtb \u6216 Mtb \u2206pknG:PknG \u682a\u611f\u67d3\u7684 U937 \u7ec6\u80de\u4e2d\uff0cTRAF2 \u548c TAK1 \u7684\u86cb\u767d\u6c34\u5e73\u663e\u8457\u964d\u4f4e\uff0c\u4f46\u5728 Mtb \u2206pknG \u6216 Mtb \u2206pknG:pknG E190A \u83cc\u682a\u79cd\u5e76\u6ca1\u6709\u964d\u4f4e\uff08\u56fe2-6 D\uff09\u3002\u8fd9\u79cd\u4f5c\u7528\u5728\u86cb\u767d\u9176\u4f53\u6291\u5236\u5242 MG132 \u5904\u7406\u7684\u7ec6\u80de\u4e2d\u88ab\u6d88\u9664\uff08\u56fe2-6E\uff09\uff0c\u4ece\u800c\u8868\u660e pknG \u4ecb\u5bfc\u7684 TRAF2 \u548c TAK1 \u86cb\u767d\u6c34\u5e73\u7684\u4e0b\u964d\u662f\u7531\u86cb\u767d\u9176\u4f53\u964d\u89e3\u5f15\u8d77\u7684\u3002<\/p>\n

      \"\"\u56fe2-6 Mtb PknG\u901a\u8fc7\u4e0eUbcH7\u7ed3\u5408\uff0c\u9776\u5411TRAF2\u548cTAK1\u964d\u89e3<\/p>\n

       <\/p>\n

      \u7efc\u4e0a\u6240\u8ff0\uff0cPknG \u53ef\u80fd\u901a\u8fc7\u4e0e UbcH7 \u76f8\u4e92\u4f5c\u7528\u4fc3\u8fdb TRAF2 \u548c TAK1 \u7684\u86cb\u767d\u9176\u4f53\u964d\u89e3\u3002<\/p>\n

      \u7814\u7a76 PknG \u5bf9 TRAF2 \u548c TAK1 \u7684 E3 \u6d3b\u6027\uff0c\u901a\u8fc7\u4f53\u5916\u6cdb\u7d20\u5316\u5b9e\u9a8c\uff0c\u5728 PknG \u6216 PknG P57A \u7a81\u53d8\u4f53\u5b58\u5728\u65f6\uff0cTRAF2 \u548c TAK1 \u660e\u663e\u6cdb\u7d20\u5316\uff0c\u4f46\u5728 PknG E190A \u7a81\u53d8\u4f53\u5b58\u5728\u65f6\uff0c\u6ca1\u6709\u6cdb\u7d20\u5316\u53d1\u751f\uff08\u56fe2-7 A\u548cB\uff09\uff0c\u4ece\u800c\u8868\u660e PknG \u62e5\u6709 E3 \u6d3b\u6027\u4fc3\u8fdb TRAF2 \u548c TAK1 \u7684\u6cdb\u7d20\u5316\u3002\u53ef\u89c1 WT PknG \u548c PknG K181M \u7a81\u53d8\u4f53\u4fc3\u8fdb\u4e86\u611f\u67d3\u5de8\u566c\u7ec6\u80de\u4e2d Ubch7 \u4f9d\u8d56\u7684 TRAF2 \u548c TAK1 \u7684\u591a\u6cdb\u7d20\u5316\uff08\u56fe2-7 C\u548cD\uff09\u3002UbcH7 \u548c Ub \u6dfb\u52a0\u5230\u7eaf\u5316\u7684 TRAF2 \u6216 TAK1 \u86cb\u767d\u4e2d\uff0c\u4fc3\u8fdb\u4e86\u5728 WT PknG \u5b58\u5728\u4e0b\u7684 TRAF2 \u6216 TAK1 \u7684\u6cdb\u7d20\u5316\uff08\u56fe2-7 E\u548cF\uff09\u3002PknG \u4fc3\u8fdb\u4e86 k48 \u8fde\u63a5\u7684 TRAF2 \u548c TAK1 \u7684\u591a\u6cdb\u7d20\u5316\uff0c\u800c\u4e0d\u662f k63 \u8fde\u63a5\u7684\u6cdb\u7d20\u5316\uff08\u56fe6G\u548cH\uff09\uff0c\u8fdb\u4e00\u6b65\u8bc1\u5b9e\u4e86 PknG \u7684\u6d3b\u6027\u4f9d\u8d56\u4e8e\u4e0e UbcH7 \u7684\u76f8\u4e92\u4f5c\u7528\uff08\u56fe2-7H\uff09\u3002<\/p>\n

      \"\"\u56fe2-7 Mtb PknG\u4f9d\u9760Ubch7\u7ed3\u5408\u4fc3\u8fdbTRAF2\u548cTAK1\u7684lys48\u8fde\u63a5\u591a\u6cdb\u7d20\u5316<\/p>\n

       <\/p>\n

      \u7efc\u4e0a\u6240\u8ff0\uff0c\u8868\u660e Mtb PknG \u901a\u8fc7\u975e\u7ecf\u5178\u7684 E1 \u548c E3 \u6d3b\u6027\u4fc3\u8fdb TRAF2 \u548c TAK1 \u6cdb\u7d20\u5316\uff0c\u6700\u7ec8\u5bfc\u81f4\u5176\u6cdb\u7d20\u5316\u964d\u89e3\u5e76\u6291\u5236 NF-\u03baB \u901a\u8def\u3002<\/p>\n

       <\/p>\n

      \u4e94\u3001Mtb PknG\u5728\u4f53\u5185\u6291\u5236\u5206\u679d\u6746\u83cc\u7684\u514d\u75ab\u5e94\u7b54<\/h3>\n

      \u6784\u5efa\u611f\u67d3 WT Mtb \u548c\u4e0d\u540c PknG \u7a81\u53d8\u4f53\u7684 Mtb \u83cc\u682a\u7684\u5c0f\u9f20\u7ed3\u6838\u6a21\u578b\uff0c\u5728\u611f\u67d3\u540e0\u30015\u300110\u300115 \u548c20\u5929\u91c7\u96c6\u80ba\u3001\u809d\u548c\u813e\u8fdb\u884c\u5206\u6790\u3002qPCR \u813e\u7ec6\u80de\u7684\u5206\u6790\u8868\u660e,\u4e0e WT \u611f\u67d3\u5c0f\u9f20\u7684\u813e\u810f\u76f8\u6bd4\uff0c\u611f\u67d3 pknG E190A \u663e\u8457\u589e\u52a0\u80bf\u7624\u574f\u6b7b\u56e0\u5b50\u548c IL-6 \u7684 mRNA \u6c34\u5e73\uff08\u56fe2-8 A\u548cB\uff09\u3002CFU \u8ba1\u6570\u548c HE \u67d3\u8272\u8bc4\u4f30\u80ba\u548c\u809d\u810f\u75c5\u7406\u53d8\u5316\uff0c\u4e0e WT Mtb \u83cc\u682a\u76f8\u6bd4\uff0c\u611f\u67d3\u540e10\u5929\uff0c\u2206pknG:pknG E190A \u83cc\u682a\u5728\u80ba\u90e8\u7684\u7ec6\u83cc\u8d1f\u8377\u548c\u80ba\u90e8\u548c\u809d\u810f\u7684\u7ec6\u80de\u6d78\u6da6\u5747\u4e0b\u964d\uff08\u56fe2-8 C\u548cD\uff09\u3002\u8fd9\u4e9b\u6570\u636e\u8868\u660e\uff0cUbcH7 \u7ed3\u5408\u4f9d\u8d56\u7684 PknG \u7684 E1 \u548c E3 \u9176\u6d3b\u6027\u6709\u52a9\u4e8e\u6291\u5236\u4f53\u5185\u5148\u5929\u514d\u75ab\u5e94\u7b54\u3002<\/p>\n

      \"\"\u56fe2-8 Mtb PknG\u5728\u4f53\u5185\u6291\u5236\u5206\u679d\u6746\u83cc\u7684\u514d\u75ab\u5e94\u7b54<\/p>\n

       <\/p>\n

      \u7efc\u4e0a\uff0c\u8be5\u6587\u521b\u65b0\u6027\u7814\u7a76\u6210\u679c\u5237\u65b0\u4e86\u5bf9\u5df2\u6709\u6cdb\u7d20\u5316\u50ac\u5316\u673a\u5236\u7684\u8ba4\u8bc6\uff0c\u63ed\u793a\u4e86\u4e00\u79cd\u75c5\u539f\u83cc\u9776\u5411\u5bbf\u4e3b\u6cdb\u7d20\u7cfb\u7edf\u7684\u65b0\u7b56\u7565\uff0c\u63d0\u4f9b\u4e86\u57fa\u4e8e\u75c5\u539f-\u5bbf\u4e3b\u754c\u9762\u7684\u6297\u7ed3\u6838\u6cbb\u7597\u65b0\u9776\u70b9\uff08\u5373 Mtb PknG \u7684\u975e\u7ecf\u5178 E1 \u548c E3 \u9176\u6d3b\u76f8\u5173\u7684 Ubl \u7ed3\u6784\u57df\uff0c\u8be5\u7ed3\u6784\u57df\u4e0e\u975e\u81f4\u75c5\u6027\u5206\u679d\u6746\u83cc\u53ca\u5bbf\u4e3b\u7ec6\u80de\u95f4\u51e0\u4e4e\u65e0\u540c\u6e90\u6027\uff09\u3002<\/p>\n

      \"\"\u56fe2-9 MtbPknG\u50ac\u5316\u975e\u7ecf\u5178\u4e24\u6b65\u6cdb\u7d20\u5316\u7ea7\u8054\u53cd\u5e94\u6291\u5236\u5bbf\u4e3b\u56fa\u6709\u514d\u75ab\u6a21\u5f0f\u56fe<\/p>\n

       <\/p>\n<\/section>\n

      \n

       <\/p>\n

      \u6676\u8bfa\u53ef\u63d0\u4f9b\u7684\u5206\u679d\u6746\u83cc-\u5bbf\u4e3b\u7ec6\u80de\u76f8\u4e92\u4f5c\u7528\u7814\u7a76\u65b9\u9762\u7684\u76f8\u5173\u5b9e\u9a8c\u5185\u5bb9\uff1a<\/p>\n

      \"\"\u5e38\u7528\u5de8\u566c\u7ec6\u80de<\/strong><\/p>\n

      THP-1\u3001Raw246.7\u7b49\u3002<\/p>\n

       <\/p>\n

       <\/p>\n

      \"\"\u5e38\u7528\u5206\u679d\u6746\u83cc<\/strong><\/p>\n

      \u803b\u57a2\u5206\u679d\u6746\u83cc\u3001BCG\u3001H37Ra\u3001H37Rv\u529f\u80fd\u57fa\u56e0\u6572\u9664\u3001\u8fc7\u8868\u8fbe\u548c\u56de\u8865\u7a81\u53d8\u4f53\u6587\u5e93\u3002<\/p>\n

       <\/p>\n

       <\/p>\n

      \"\"\u7814\u7a76\u5185\u5bb9<\/strong><\/p>\n

      \u7ed3\u6838\u83cc-\u5bbf\u4e3b\u4e92\u4f5c\uff08\u7ed3\u6838\u83cc\u67d0\u57fa\u56e0\u4f5c\u7528\uff09\u3001\u67d0\u57fa\u56e0\u4e0e\u6613\u611f\u6027\u7814\u7a76\u3001\u836f\u7269\u4f5c\u7528\u7b49\u65b9\u9762\u3002<\/p>\n

       <\/p>\n

       <\/p>\n

      \"\"<\/p>\n

      \u6b22\u8fce\u5404\u4f4d\u8001\u5e08\u4ea4\u6d41\u548c\u54a8\u8be2<\/p>\n

       <\/p>\n

      \n

       <\/p>\n

      \u6587\u7ae0\u94fe\u63a5<\/p>\n[1] New insights into the evasion of host innate immunity by Mycobacterium tuberculosis<\/p>\n

      https:\/\/www.nature.com\/articles\/s41423-020-0502-z<\/p>\n[2] Mycobacterium tuberculosis protein kinase G acts as an unusual ubiquitinating enzyme to impair host immunity<\/p>\n

      https:\/\/www.embopress.org\/doi\/epdf\/10.15252\/embr.202052175<\/p>\n

       <\/p>\n

      \n

       <\/p>\n

      \u8054\u7cfb\u6211\u4eec<\/p>\n

      \u7535\u8bdd\uff1a13392273325\uff08\u5fae\u4fe1\uff09<\/p>\n

      Q Q\uff1a2775427010<\/p>\n

      \u4e1a\u52a1\uff1ainfo@gene-optimal.com<\/p>\n

      \u62db\u8058\uff1ahr@gene-optimal.com<\/p>\n

      \u4e0a\u6d77\uff1a\u5f20\u6c5f\u8521\u4f26\u8def780\u53f74\u697cA\u5ea7<\/p>\n

      \u5e7f\u4e1c\uff1a\u4f5b\u5c71\u5cad\u5357\u5927\u90532\u53f7\u4e2d\u6b27\u4e2d\u5fc3A\u680b3\u697c<\/p>\n

      \u7f51\u7ad9\uff1awww.gene-optimal.com<\/p>\n

       <\/p>\n

      \"\"<\/p>\n","protected":false},"excerpt":{"rendered":"

      \u7ed3\u6838\u5206\u679d\u6746\u83cc\u662f\u4e00\u79cd\u80de\u5185\u75c5\u539f\u83cc\uff0c\u80fd\u591f\u8fd0\u7528\u591a\u79cd\u7b56\u7565\u5e72\u9884…<\/p>\n","protected":false},"author":1,"featured_media":45033,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[4],"tags":[],"_links":{"self":[{"href":"https:\/\/www.gene-optimal.com\/wp-json\/wp\/v2\/posts\/45011"}],"collection":[{"href":"https:\/\/www.gene-optimal.com\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.gene-optimal.com\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.gene-optimal.com\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/www.gene-optimal.com\/wp-json\/wp\/v2\/comments?post=45011"}],"version-history":[{"count":7,"href":"https:\/\/www.gene-optimal.com\/wp-json\/wp\/v2\/posts\/45011\/revisions"}],"predecessor-version":[{"id":45039,"href":"https:\/\/www.gene-optimal.com\/wp-json\/wp\/v2\/posts\/45011\/revisions\/45039"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.gene-optimal.com\/wp-json\/wp\/v2\/media\/45033"}],"wp:attachment":[{"href":"https:\/\/www.gene-optimal.com\/wp-json\/wp\/v2\/media?parent=45011"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.gene-optimal.com\/wp-json\/wp\/v2\/categories?post=45011"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.gene-optimal.com\/wp-json\/wp\/v2\/tags?post=45011"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}