Please use this identifier to cite or link to this item: http://hdl.handle.net/11455/66299
DC FieldValueLanguage
dc.contributor張登欽zh_TW
dc.contributor宣詩玲zh_TW
dc.contributor邱政洵zh_TW
dc.contributor朱純燕zh_TW
dc.contributor葉光勝zh_TW
dc.contributor.advisor簡茂盛zh_TW
dc.contributor.author陳正文zh_TW
dc.contributor.authorChen, Zeng-Wengen_US
dc.contributor.other中興大學zh_TW
dc.date2012zh_TW
dc.date.accessioned2014-06-09T09:31:19Z-
dc.date.available2014-06-09T09:31:19Z-
dc.identifierU0005-1901201111573600zh_TW
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dc.identifier.urihttp://hdl.handle.net/11455/66299-
dc.description.abstract豬沙門氏桿菌症(salmonellosis)是豬隻重要細菌性疾病之一。眾多沙門氏桿菌血清型中,豬霍亂沙門氏桿菌(Salmonella Choleraesuis)因會造成豬隻敗血症而受到重視。沙門氏桿菌症的預防上,活毒減毒疫苗是預防此疾病最有效的方法之一。根據文獻得知,具有cAMP受體蛋白(cAMP receptor protein; CRP)基因突變的豬霍亂沙門氏桿菌,不僅呈現高度減毒且可引起宿主良好免疫反應的菌株,該菌株常被應用在沙門氏桿菌疫苗的開發上,然而其毒力減弱的機轉仍尚未被瞭解。因此本研究之目的即是構築一豬霍亂沙門氏桿菌crp突變株,並探討crp突變株的減毒機制。研究結果顯示,豬霍亂沙門氏桿菌crp基因剔除後,突變菌株對於酸性環境及膽鹽,反而較親代株具有更高的耐受性,顯示此兩種殺菌條件與crp突變株的毒力減弱無關。而以豬隻ligated ileal loop動物實驗模式評估細菌入侵能力之結果發現,crp突變株在迴腸上皮及腸繫膜淋巴結的入侵能力,卻明顯較親代株降低。此外,沙門氏桿菌的腸道入侵與第三型分泌系統 (Salmonella pathogenicity island 1 (SPI-1) encoded type III secretion system; SPI-1 T3SS)有密切關係,因此本研究亦針對SPI-1 T3SS的分泌功能進行檢驗。結果顯示,crp突變株之SPI-1 T3SS無法正常分泌與細菌入侵有關的SopB (Salmonell outer protein B)分泌蛋白,且與巨噬細胞死亡(pyrotosis)有關SipB (Salmonella invasion protein B)蛋白之分泌,亦同時受到抑制。以上研究結果顯示,豬霍亂沙門氏桿菌crp基因突變後,SPI-1 T3SS之分泌功能會受到抑制,而相關所造成的腸道入侵能力減低及巨噬細胞死亡的減少,是豬霍亂沙門氏桿菌crp突變株毒力減弱的原因之一。zh_TW
dc.description.abstractSalmonella enterica serovar Choleraesuis (S. Choleraesuis) causes a lethal systemic infection (salmonellosis) in swine. Live attenuated S. Choleraesuis vaccines are effective in preventing the disease, and isolates of S. Choleraesuis with mutations in the cAMP receptor protein (CRP) gene (S. Choleraesuis ∆crp) are the most widely used, although the basis of the attenuation remains unclear. The objectives of this study were to construct a S. Choleraesuis crp gene mutant and to determine whether the attenuated phenotype of S. Choleraesuis ∆crp was due to alterations in susceptibility to gastrointestinal factors such as pH and bile salts, ability to colonize or invade the intestine, or cytotoxicity for macrophages. The results indicated that, although the survival of S. Choleraesuis ∆crp at low pH or in the presence of bile salts did not differ significantly from the parental strain, the ability of the mutant to invade intestinal epithelia was significantly decreased. In examining the role of CRP on the secretory function of the Salmonella pathogenicity island 1 (SPI-1) encoded type III secretion system (T3SS), it was found that S. Choleraesuis ∆crp was unable to secrete the SPI-1 T3SS effector proteins, SopB and SipB, which play an important role in Salmonella intestinal invasiveness and macrophage cytotoxicity, respectively. In addition, caspase-1 dependent cytotoxicity for macrophages was significantly reduced in S. Choleraesuis ∆crp. Collectively, this study demonstrated that the CRP affects the secretory function of SPI-1 T3SS resulting in reduced ability to invade host intestinal epithelium that is a critical element in the pathogenesis of S. Choleraesuis.en_US
dc.description.tableofcontents中文摘要 ----------------------------------------------------------------------------------- 3 英文摘要 ----------------------------------------------------------------------------------- 4 目 次 ----------------------------------------------------------------------------------- 5 表 次 ----------------------------------------------------------------------------------- 8 圖 次 ----------------------------------------------------------------------------------- 9 第一章 前言----------------------------------------------------------------------------- 11 第二章 文獻探討---------------------------------------------------------------------- 12 第一節 沙門氏桿菌細菌簡介、血清型分類及命名------------------------- 12 第二節 生化特性及培養------------------------------------------------------- 12 第三節 流行病學--------------------------------------------------------------- 13 第四節 沙門氏桿菌與公共衛生------------------------------------------------ 14 第五節 沙門氏桿菌症--------------------------------------------------------- 15 第六節 豬沙門氏桿菌症------------------------------------------------------- 16 第七節 宿主與沙門氏桿菌---------------------------------------------------------- 17 一 沙門氏桿菌引起之下痢症機制探討--------------------------------- 17 二 沙門氏桿菌全身性感染之機制探討--------------------------------- 18 第八節 第三型分泌系統(Type III Secretion System; T3SS)----------------- 20 一 T3SS的結構與功能--------------------------------------------------- 20 二 沙門氏桿菌T3SS分泌蛋白(effector proteins)及其功能------------ 21 (一) 與細菌入侵細胞相關之T3SS分泌蛋白----------------------------- 21 (二) 與Salmonella containing vacuole (SCV)相關之T3SS分泌蛋白--- 22 (三) SCV位置調控與Salmonella-induced filaments相關之T3SS分泌蛋白--------------------------------------------------------------------24 (四) 具炎症反應調控及引起巨噬細胞死亡之T3SS分泌蛋白----------- 25 第九節 沙門氏桿菌與Inflammasomes之關係------------------------------- 27 一 Pattern- recognition receptors (PRRs)-------------------------------- 27 二 沙門氏桿菌引起caspase-1活化機制探討-------------------------- 28 第十節 沙門氏桿菌症之防治------------------------------------------------- 29 第十一節 cAMP receptor protein (CRP)----------------------------------------- 30 一 CRP蛋白基因及其表現調控----------------------------------------- 30 二 CRP蛋白對細菌基因的調控機制------------------------------------ 31 三 CRP蛋白與細菌致病因子調控--------------------------------------- 32 第三章 材料與方法------------------------------------------------------------------- 33 第一節 無抗藥性基因之Salmonella Choleraesuis crp 突變株之構築原理---------------------------------------------------------------------------------- 33 第二節 菌株來源、質體及引子對-------------------------------------------------- 34 第三節 自殺載體之構築------------------------------------------------------------- 34 第四節 突變菌株之選殖------------------------------------------------------------- 34 第五節 南方墨點法(Southern blotting)-------------------------------------------- 35 一 探針之製備及定量---------------------------------------------------------- 35 二 細菌基因體DNA之限制酵素切割及電泳----------------------------- 36 三 毛細轉漬法(capillary transfer)--------------------------------------------- 36 第六節 互補質體之構築------------------------------------------------------------- 38 一 互補試驗原理---------------------------------------------------------------- 38 二 互補質體構築方法---------------------------------------------------------- 38 第七節 突變菌株之表現型生化鑑定---------------------------------------------- 38 第八節 Salmonella Choleraesuis crp突變株減毒能力之探討----------------- 39 一 小鼠LD50試驗--------------------------------------------------------------- 39 二 試管內細菌存活試驗------------------------------------------------------- 39 三 Ligated ileal loop試驗------------------------------------------------------ 40 四 HeLa Cell感染試驗--------------------------------------------------------- 41 五 沙門氏桿菌於巨噬細胞之存活試驗------------------------------------- 42 六 SopB,SipB及SifB表現質體之構築----------------------------------- 43 七 SPI-1第三型分泌系統之功能測試--------------------------------------- 44 八 SPI-2第三型分泌系統之功能試驗--------------------------------------- 45 九 沙門氏桿菌於巨噬細胞之細胞毒性試驗------------------------------- 45 第四章 結果----------------------------------------------------------------------------- 47 第一節 無抗藥性Salmonella Choleraesuis crp突變株之構築----------------- 47 第二節 crp互補質體之構築及互補試驗------------------------------------------ 48 第三節 Salmonella Choleraesuis crp基因突變菌株於小鼠之半致死劑量測定------------------------------------------------------------------------------- 48 第四節 酸及膽鹽對於Salmonella Choleraesuis crp基因突變菌株之影響-- 49 第五節 crp基因突變菌株於腸道侵入(invasion)之情形------------------------ 50 第六節 crp基因突變菌株於豬肺臟巨噬細胞之侵入及存活情形------------ 51 第七節 crp基因突變菌株無法分泌SPI-1 T3SS分泌蛋白-------------------- 51 第八節 沙門氏桿菌crp基因突變菌株引起較弱的巨噬細胞毒性反應----- 53 第五章 討論----------------------------------------------------------------------------- 55zh_TW
dc.language.isoen_USzh_TW
dc.publisher微生物暨公共衛生學研究所zh_TW
dc.relation.urihttp://www.airitilibrary.com/Publication/alDetailedMesh1?DocID=U0005-1901201111573600en_US
dc.subjectSalmonellaen_US
dc.subject沙門氏桿菌zh_TW
dc.subjectType Three Secretion Systemen_US
dc.subjectCRPen_US
dc.subjectcAMP receptor proteinen_US
dc.subject第三型分泌系統zh_TW
dc.subjectCRPzh_TW
dc.subjectcAMP receptor proteinzh_TW
dc.title豬霍亂沙門氏桿菌cAMP受體蛋白對第三型分泌系統之功能性調控作用zh_TW
dc.titleEffect of cAMP Receptor Protein on Regulation of Type III Secretion System of Salmonella enterica Serotype Choleraesuisen_US
dc.typeThesis and Dissertationzh_TW
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