胃幽門螺旋桿菌感染了全世界約50%的人口，感染此菌後可能會導致胃炎﹑消化性潰
瘍或是增加罹患胃腺癌的機率，而詳細的感染機制和長久感染的原因都尚未清楚，因
此，找尋一個關鍵的致病因子來設計相關藥物對於治療胃幽門螺旋桿菌感染是很重要
的。BabA 為第一個發現有黏附能力的外膜蛋白且已被證實能夠和宿主細胞上的Lewis b
鍵結。脂多醣體為格蘭氏陰性菌外膜上特有的結構，主要是由脂質A﹑核心寡糖(包括
外核與內核)與O 抗原所組成，其功能為維持外膜的穩定性與刺激宿主細胞的免疫反
應。在先前的研究中，我們已確認HP0859 參與了脂多醣內核生合成，令人驚訝地，當
我們剃除HP0859 後不只會縮短脂多醣體的結構同時也會使許多重要黏附蛋白的分子量
變小，我們推測HP0859 的剃除可能會影響到這些黏附蛋白的醣化修飾，而黏附蛋白的
醣化修飾對於胃幽門螺旋桿菌的貼附能力是非常重要的。在此研究中，我們建構了Δ0859,
ΔBabA 與Δ0859/ΔBabA 突變菌株並且分析相關的貼附能力與致病力，有趣的是，黏附
蛋白BabA 在HP0859 突變菌株中的分子量的確是比較小的，另外，HP0859 突變菌株與
HP0859/BabA 雙重突變菌株的外膜通透性與疏水性都有顯著的上升，而在BabA 基因剃
除的菌株中可以看見隨著靜置時間的增加其疏水性也有增加的現象，此外我們也發現在
BabA 突變菌株中脂多醣體的O 抗原部分缺少了Lewis x，但BabA 突變菌株在貼附能力
與毒素蛋白CagA 的注入都只有部分的減少，而HP0859 突變菌株與HP0859/BabA 雙重
突變菌株都明顯的失去了貼附能力與毒素蛋白CagA 的注入。這些實驗結果均暗示著胃
幽門螺旋桿菌需要緊密的貼附上宿主細胞，才能夠形成第四型分泌系統來注入毒素蛋白
CagA，因此剔除掉單一重要黏附蛋白並無法有效的抑制胃幽門螺旋桿菌感染。相反的，
剃除掉脂多醣內核生合成基因HP0859，能夠改變許多重要貼附蛋白(包含BabA)的醣化
並使貼附能力有顯著性的降低，進而有效的抑制胃幽門螺旋桿菌的感染。

Helicobacter pylori (H. pylori) infects more than 50% of the world population and
results in gastritis, peptic ulceration and gastric adenocarcinoma. In spite of the identification
of numerous virulence factors, the detailed mechanism of pathogenesis and long-term
infection of this bacterium remain illusive. Therefore, finding a key gene of virulence and
pathogenicity is important for generating a treatment against H. pylori infection. BabA is the
first adhesin found in H. pylori and has been demonstrated to bind to Lewis b.
Lipopolysaccharide (LPS) is essential for the physical integrity of the outer membrane in
Gram-negative bacteria and plays an important role in immunostimulation of the infected
hosts. It is composed of lipid A, core oligosaccharide (including inner core and outer core)
and O-antigen. Previously, our laboratory had identified HP0859 is involved in the
biosynthesis of H. pylori LPS inner core. Surprisingly, the knockout of HP0859 not only
shortens the LPS structure but also decreases the molecule weight of several key adhesins. We
proposed that the disruption of HP0859 alters the glycosylation status of adhesins, and the
glycosylation of key adhesins plays a vital role in H. pylori adhesion. In this study, we
constructed the corresponding mutants and tested the adhesion and pathogenesis ability of WT,
Δ0859, ΔBabA and Δ0859/ΔBabA. Interestingly, the molecular size of BabA was indeed
reduced in Δ0859. The permeability and hydrophobicity of outer membrane were significantly
increased in Δ0859 and Δ0859/ΔBabA, and the hydrophobicity in ΔBabA was slightly
increased along with the increasing time of standing. We also found that ΔBabA lacked Lewis
x in the O-antigen of LPS. In comparison, ΔBabA lost only a part of adhesion ability and
CagA translocation, but Δ0859 and Δ0859/ΔBabA markedly abolished these abilities. This
observation implied that H. pylori requires tight adhesion to host cells to promote the
formation of type IV secretion system (T4SS) to inject the Cag A, and the disruption of bab A
expression will not completely inhibit H. pylori adhesion. In contrast, the disruption of HP0859 gene involved in the LPS inner core biosynthesis can alter the glycosylation status in
all of the key adhesins (including BabA) and thus significantly reduce H. pylori adhesion.

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