出血性大腸桿菌為革蘭氏陰性菌，其主要血清型為O157:H7，其會經由食物或水源傳播感染，當病人受到出血性大腸桿菌感染時，可能會導致腹瀉、溶血性尿毒症甚至是腎衰竭等症狀。在之前的研究中，我們發現秀麗隱桿線蟲(Caenorhabditis elegans)會被出血性大腸桿菌感染及毒殺，此外，也發現此致病菌會在線蟲的腸道當中寄殖及複製。過去的許多研究中已經找到了出血性大腸桿菌參與寄殖的主要因子，然而對於參與其中的宿主因子仍是值得被研究的部分。在我們的研究當中，我們利用甲基磺酸乙酯(EMS)突變劑去篩選對於出血性大腸桿菌寄殖於線蟲所參與的宿主因子。
經由甲基磺酸乙酯作用後的突變株，我們共篩選出32株突變株具有”腸道寄殖增加”(enhanced intestinal colonization, INC)的表現型，在第二次篩選中，我們餵食這32株突變株帶有綠色螢光(GFP)的出血性大腸桿菌，再次確認其腸道內螢光表現增加的情況。接著，我們測試這些突變株對於出血性大腸桿菌感染是否有不同的感受性，其結果令我們驚訝的是其中四株突變株擁有INC的表現型，卻對於出血性大腸桿菌有較強的抵抗能力，這個現象違背我們對於細菌感染的現有知識，因此，我們利用傳統遺傳學方法及單核苷酸多態性分析方法(SNP mapping)分析這四株突變株，經由初步結果，品種YQ087的突變區位在染色體V上，其他三株突變株YQ032、YQ139、YQ106的突變區皆位在染色體I上，且其突變範圍位在基因位置-6到+5之間。我們相信藉由瞭解參與出血性大腸桿菌感染宿主時所需的宿主因子及其功能，可為線蟲抵禦出血性大腸桿菌感染之研究帶來新的曙光。

Enterohemorrhagic E. coli (EHEC), the major serotype is O157:H7, is a gram-negative rod-shaped bacterium that causes illness through water and food. Patients infected by EHEC may lead to hemorrhagic diarrhea and hemolytic uremic syndrome. In our previous study, we found that E. coli O157:H7 strain EDL933 infected and killed C. elegans animals. Moreover, EHEC colonizes and replicates in the intestinal lumen of C. elegans. Several published literatures have identified the key bacterial factors required for E. coli O157:H7 colonization, however the host factors involved in EHEC colonization remain understudied. Here, we applied the EMS-mediated forward genetic screen for identifying the host factors involved in EHEC colonization in C. elegans.
We have isolated 32 EMS (Ethyl methanesulfonate)-induced mutants conferred the INC (enhanced intestinal colonization) phenotype. The INC phenotype of these mutants was reconfirmed by a secondary screen fed with the GFP-labeled EHEC. We then examined whether these mutants exhibit different host susceptibility to EHEC infection. To our surprise, four mutants with the INC phenotype exhibited a significant EHEC resistant phenotype compared to the wild-type N2 animals. Given that the mutation alleles in these four mutants enhance the EHEC intestinal colonization yet confer resistance to EHEC infection, this phenomenon is contradictory to our current knowledge about bacterial infection. We therefore turned our attentions to identify the identities of these alleles by conventional two-point mapping and SNP (single-nucleotide polymorphism) mapping. The preliminary results showed the mutation locus of one strain YQ087 is located on chromosome V, and the other three strains YQ139, YQ032 and YQ106 are located on chromosome I, ranging between genetic location -6 to +5. We believe through our study on the function of the host factors required for EHEC colonization and infection may gain insights on the novel aspects of immunity in EHEC infection.

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