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首页> 外文期刊>Infection and immunity >Expression of Sialylated or Paragloboside-Like Lipooligosaccharides Are Not Required for Pustule Formation byHaemophilus ducreyi in Human Volunteers
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Expression of Sialylated or Paragloboside-Like Lipooligosaccharides Are Not Required for Pustule Formation byHaemophilus ducreyi in Human Volunteers

机译:唾液形或嗜珠状糖脂样低聚糖的表达对于人类志愿者中的杜克嗜血杆菌形成脓疱并不需要

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The lipooligosaccharide (LOS) of Haemophilus ducreyi, the etiologic agent of chancroid, chemically and immunologically resembles human glycosphingolipid antigens. To test whether LOS that contains paragloboside-like structures was required for pustule formation, an isogenic mutant (35000HP-RSM2) was constructed inlosB, which encodesd-glycero-d-manno-heptosyltransferase. 35000HP-RSM2 produces a truncated LOS whose major glycoform terminates in a single glucose attached to a heptose trisaccharide core and 2-keto-3-deoxyoctulosonic acid. Five human subjects were inoculated with 35000HP and 35000HP-RSM2 in a dose-response trial. For estimated delivered doses (EDDs) of ≥25 CFU, the pustule formation rates were 80% for 35000HP and 58% for 35000HP-RSM2. Preliminary data indicated that a previously described Tn916 losB mutant made a minor glycoform that does not require dd-heptose to form the terminal N-acetyllactosamine. If 35000HP-RSM2 made this glycoform, then 35000HP-RSM2 could theoretically make a sialylated glycoform. To test whether sialylated LOS was required for pustule formation, a second trial comparing an isogenic sialyltransferase mutant (35000HP-RSM203) to 35000HP was performed in five additional subjects. For EDDs of ≥25 CFU, the pustule formation rates were 30% for both 35000HP and 35000HP-RSM203. The histopathology and recovery rates of H. ducreyi from surface cultures and biopsies obtained from mutant and parent sites in both trials were similar. These results indicate that neither the expression of a major glycoform resembling paragloboside nor sialylated LOS is required for pustule formation by H. ducreyi in humans.
机译:拟螺旋体的病原体 Haemophilus ducreyi 的脂寡糖在化学和免疫学上类似于人糖鞘脂抗原。为了测试是否需要形成含有副球蛋白样结构的LOS,以形成脓疱,在 losB 中构建了一个等基因突变体(35000HP-RSM2),该突变体编码d- 甘油 -d- manno -庚糖基转移酶。 35000HP-RSM2产生截短的LOS,其主要糖型终止于连接到庚糖三糖核心和2-酮-3-脱氧辛酸的单个葡萄糖。在剂量反应试验中,向五名人类受试者接种了35000HP和35000HP-RSM2。对于≥25 CFU的估计输送剂量(EDD),35000HP的脓疱形成率为80%,35000HP-RSM2的脓疱形成率为58%。初步数据表明,先前描述的Tn 916 losB 突变体形成了较小的糖型,不需要dd-庚糖即可形成末端 N -乙酰基乳糖胺。如果35000HP-RSM2产生这种糖型,那么35000HP-RSM2在理论上可以制造出唾液酸化的糖型。为了测试脓疱形成是否需要唾液酸化的LOS,在另外五个受试者中进行了第二项比较同基因唾液酸转移酶突变体(35000HP-RSM203)与35000HP的试验。对于EDD≥25 CFU,35000HP和35000HP-RSM203的脓疱形成率均为30%。 H的组织病理学和恢复率。在两个试验中,来自表面培养物的ducreyi 和从突变位点和亲本位点获得的活组织检查都相似。这些结果表明,由 H形成脓疱既不需要类似于副球糖苷的主要糖型的表达,也不要求唾液酸化的LOS的唾液酸化。人类中的ducreyi

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