幽門桿菌為相當重要之人類的胃致病菌，而細菌附著又為感染胃部黏膜之第一步。許多附著因子如熱休克蛋白質、BabA、AlpAB、Hop 系列蛋白質、OipA、SabA 及 Lewis x 等與幽門桿菌的附著有關，其中又以 BabA 與宿主細胞 Leb 結合的研究較為清楚。為探討本地菌株 BabA 與 Leb 結合於組織變化的角色，本研究收集胃組織與其感染之細菌，以觀察細菌 babA2 的表現與胃組織 Le 抗原的相關性。結果顯示所有菌株皆具有 babA2，胃組織表現 Leb 相較於無 Leb 表現的病人，其具有較高的幽門桿菌總菌落量 (HPD) (p < 0.001) 與慢性發炎指數 (p < 0.05)，Leb 表現的強度也與 HPD 呈現正相關且是影響 HPD 的獨立因子 (p < 0.05)。49 位無 Leb 表現的病人，其表現 Lea 與 Lex 者有較高 HPD 且多變項邏輯分析也顯示 Lea 與 Lex 為獨立的影響因子 (p < 0.05)，當病人因幽門腺體委縮 (antral atrophy) 而 Leb 表現下降時，Lex 於胃體 (corpus) 及賁門 (cardia) 的表現上升以維持菌量 (p < 0.05)。為進而釐清細菌所表現之 Lex 抗原的功能，則以 anti-Le 抗原的抗體作用於幽門桿菌菌株，發現只有 anti-Lex 而不是 anti-Leb 及 anti-Ley 單株抗體 (MAb)，能增加表現高 Lex 抗原的細菌對於 AGS 細胞的附著能力，而這增加附著的現象並不會發生於表現低 Lex 抗原的細菌。Anti-Lex MAb 可以增加野生株及其 babA2 突變株對於 AGS 細胞的附著能力，當 AGS 細胞前處理 anti-Lex MAb 時，babA2 突變株的附著情況也是增加的，也只有 anti-Lex MAb 可以促進細菌的聚集，且原位附著實驗更進一步確認 anti-Lex MAb 使得細菌更密集的附著於來自臨床病人的胃上皮細胞，這些結果意謂著 anti-Lex MAb 透過促進細菌聚集及成為細菌與宿主間橋樑的機制，可以專一性的增加幽門桿菌之附著能力。
另一方面，在台灣多重幽門桿菌菌株感染之盛行率尚未清楚的情況下，值得分析台灣地區病人是否有多重菌株的感染且是否會影響毒力因子 (如 CagA) 與疾病的表現。本研究從 30 位病人之胃幽門與胃體各分離 4-8 個幽門桿菌菌落，以 random amplified polymorphic DNA profiles 區分菌株的基因差異性及西方點墨法偵測 CagA 磷酸化的程度，結果發現 23.3% (7/30) 的病人具有多重菌株感染且胃幽門與胃體兩部位各自有一主要感染的菌株。於 23 個單一細菌感染的病人中，發現胃幽門之急性發炎指數、慢性發炎指數、胃萎縮與淋巴球聚集都較胃體來得嚴重 (p <= 0.002)，然而七位多重菌株感染病人之胃幽門與胃體的慢性發炎指數、菌落量、胃萎縮及淋巴球聚集等指數是相似的 (p > 0.05)。多重菌株相較於單一菌株感染之病人，於胃體有些微較高之慢性發炎指數與菌落量 (p = 0.062 and p = 0.095) 且與胃幽門部位腸化生的發生有關 (p = 0.005)。我們進一步分析附著因子與抗酸性，對菌株於胃之分佈的影響，初步的結果顯示 BabA 的相似性蛋白質與抗酸性，對於菌株分佈具有一些角色。另一方面，四位多重菌株感染的病人以其胃幽門與胃體 4-5 株的菌株感染細胞，發現 CagA 磷酸化的程度會受 CagA 的序列、菌體本身 CagA 產量及其他因素的影響。以上結果顯示多重幽門桿菌感染人體胃部時具有組織特異性，且會改變胃幽門與胃體間之組織變化的差異，也與胃幽門腸化生的發生有關，而 CagA 磷酸化的程度則有多個機制參與。

Helicobacter pylori is an important human gastric pathogen. Bacterial adhesion is a prerequisite for colonizing the gastric mucosal surfaces. Many adhesin molecules, such as heat shock proteins, BabA, AlpAB, Hop proteins family, OipA, SabA and Lewis x (Lex) suggested to be involved in the initial colonization of H. pylori. Several investigators have extensively studied the relation between BabA and Leb antigen of host cell. In order to understand the histological role of BabA and Leb interaction in our clinical strains, we collected the gastric tissues and bacteria to analyze the correlation between the babA2 and the Le antigens on gastric tissues. The data showed that all H. pylori isolates had a positive babA2 genotype. The patients with gastric Leb expression had higher the total density of H. pylori (HPD) (p < 0.001) and chronic inflammation score (p < 0.05) than those without Leb expression. The intensity of Leb also had positive corelation with HPD and was an independent factor to affect HPD (p < 0.05). For the 49 patients without gastric Leb expression, those with Lex and Lea expression had higher HPD and Lex and Lea were independent factor to affect HPD (p < 0.05). When the stomach of patients had antral atrophy to decrease the intensity of Leb, a significant increase of the intensity of Lex over the gastric corpus and cardia maintained the bacterial density (p < 0.05). In order to demonstrate the function of bacterial Lex antigen, H. pylori was treated with anti-Le Ab and revealed that an anti-Lex MAb, but not anti-Leb MAb or anti-Ley MAb, could enhance the adhesion of H. pylori strains which expressed high levels of Lex antigen to AGS cells. The adhesion enhancement was not found on H. pylori strain with low level of Lex antigen. Anti-Lex MAb could increase the adhesion of both the wild-type strain and its isogenic babA2 mutant to AGS cells. When AGS cells were pretreated with anti-Lex MAb, the adhesion of the babA2 mutant also increased. Only anti-Lex MAb could promote bacterial agglutination, and the in situ adhesion assay further confirmed that adding anti-Lex MAb resulted in denser bacterial adhesion on the gastric epithelium collected from clinical patients. These results suggest anti-Lex MAb could specifically enhance the adhesion ability of H. pylori strains through a mechanism by which anti-Lex MAb promotes bacterial aggregation and mediates bivalent interaction (antigen-antibody-antigen) between bacteria and host cells.
The prevalence of mixed H. pylori infection in Taiwan is not clear. It is worth to investigate whether Taiwanese patients were infected by mixed H. pylori strains and it would affect virulence factors (such as CagA) and disease outcomes. We isolated H. pylori from the antrum and the corpus of 30 dyspeptic patients. Four to eight colonies were randomly collected from each site. The genetic diversity of each isolate was compared by random amplified polymorphic DNA profiles. The phosphorylation level of CagA was analyzed by Western blotting. We found the prevalence of mixed infections was 23.3% (7/30) and different dominant strains were isolated from the antrum and the corpus specimens. In the 23 patients with single strain infections, the acute inflammation score (AIS), chronic inflammation score (CIS), atrophy (AT) and lymphoid follicle (LF) of the antrum were usually more severe than those of the corpus (p <= 0.002). However, for the 7 patients with mixed infections, there were similar CIS, H. pylori density (HPD), AT and LF between the antrum and the corpus (p > 0.05). Moreover, the patients with mixed infections had marginally higher CIS and HPD than those with single infection (p = 0.062 and p = 0.095) in the corpus and had a significantly higher rate of the appearance of intestinal metaplasia (IM) in the antrum (p = 0.005). We further detected the effects of the adhesin expression and acid resistance ability of the strain on gastric distribution. Our preliminary data showed that BabA similar protein and acid resistance ability played some role on strain distribution. In addition, 4-5 isolates of the antrum and the corpus from each of 4 patients with mixed infection infected AGS cells. We found that the CagA phosphorylation was affected by bacterial cagA sequence, its expression and others. These data show that mixed H. pylori strains infecting human stomach have tissue tropism, which could change the histological difference between the antrum and the corpus, and be also associated with the appearance of IM in the antrum. Moreover, there could be many mechanisms involved in the CagA phosphorylation.

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