出血性大腸桿菌是一種經由食物傳染的致病性大腸桿菌。我們實驗室以模式生物秀麗線蟲作為宿主，研究出血性大腸桿菌以及其宿主之間的交互作用。過去研究發現出血性大腸桿菌可以在線蟲腸道內增生並導致線蟲壽命減短；並發現參與脂多醣合成的基因包括rfaD突變時會讓其毒力大大地降低。為了瞭解線蟲如何反應出血性大腸桿菌的感染，我們採取觀察線蟲轉錄體的變化及進行功能性篩選這兩個策略進行研究。利用次世代定序分析當秀麗線蟲在餵食出血性大腸桿菌EDL933或rfaD被突變的出血性大腸桿菌六小時內其轉譯體的變化。經由分析發現許多膠原蛋白會被EDL933誘導表現，許多UDP-葡萄糖醛酸/ UDP-葡萄糖轉移酶和細胞色素P450會被EDL933抑制表現。EDL933可以經由抑制cyp-35A3及cyp-35A4削弱線蟲對EDL933的抵抗力。另一方面，許多物種可以利用模式識別受體辨識病原體相關分子模式使宿主可以抵抗致病菌。為了瞭解線蟲是否擁有模式識別受體，我們利用RNAi篩選在其他物種具有模式識別受體功能的蛋白家族成員，篩選的結果發現有7個基因會降低線蟲對於出血性大腸桿菌的抵抗能力。其中iglr-2可以在線蟲發育成熟後影響其對EDL933的抵抗力。經由生理的觀察以及測試其對壓力的反應，發現iglr-2被抑制並不會造成線蟲發育上的缺陷或使牠原本比較脆弱，並且會影響線蟲對其他許多致病菌的抵抗力。但抑制iglr-2會造成線蟲提早老化及壽命的縮短；因此，抑制iglr-2所造成的影響是必須釐清的。而對於其他基因如何影響線蟲的抵抗力仍需進一步的研究。

Enterohaemorrhagic Escherichia coli, EHEC, is a food-borne pathogenic E. coli. Our laboratory uses Caenorhabditis elegans as an animal model to study the interaction between EHEC and its host. Previous study revealed that EHEC can colonize in lumen of C. elegans and shorten its lifespan; we found that the mutation of genes involved in lipopolysaccharide biosynthesis, including rfaD, depresses the toxicity of EHEC significantly. In order to understand the response of C. elegans against EHEC infection, we study our subject by tow strategies: analyzing changes in transcriptome of C. elegans and functional screening. By a next generation sequencing, we analyzed the changes in transcriptomes of C. elegans fed with EHEC EDL933 and EDL933 rfaD mutant for 6 hours. Sequencing results showed that many genes in the collagen were induced by EDL933; many genes in UDPGT and cytochrome P450 were depressed. EDL933 can impair the resistance of C. elegans by depressing cyp-35A3 and cyp-35A4 expression. On the other hand, many species detect pathogen by pattern-recognition receptor (PRR) recognizing the pathogen-associated molecular pattern. To identify the PRR in C. elegans, we screened the protein families with known function of pathogen detection in other species. By the RNAi screenging, 7 genes were discovered to depress the resistance of C. elegans against EDL933. Among them, iglr-2 can influence the resistance against EHEC after mature of C.elegans. By the physiological observation and stress test, we found that depression of iglr-2 does not make C. elegans defect or general weak; it also influence the resistance of C. elegans against many other pathogen. However, iglr-2 depression promotes aging and shortens lifespan. Therefore, the effects of iglr-2 knockdown have to be clarified. The impact of other genes on the resistance of C. elegans against EHEC remains more studies.

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