Enterotoxigenic Escherichia coli-blood group A interactions intensify diarrheal severity
Enterotoxigenic Escherichia coli-blood group A interactions intensify diarrheal severity
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DOI：
10.1172/jci97659
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发表时间：
2018-08-01
影响因子：
15.9
通讯作者：
Fleckenstein, James M.
中科院分区：
文献类型：
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作者：
Kumar, Pardeep;Kuhlmann, F. Matthew;Fleckenstein, James M.
产肠毒素大肠杆菌(ETEC)感染在发展中国家非常普遍，这些国家的临床表现从无症状的定植到严重的霍乱样疾病。这些不同的表现可能涉及菌株特定的毒力特征以及宿主因素，其分子基础尚未阐明。我们证明，当受到ETEC菌株H10407的攻击时，A型人类志愿者比其他血型的人更容易出现严重腹泻。有趣的是，包括H10407在内的多种ETEC菌株都能分泌EtpA粘附素分子。由于许多细菌粘附素也凝集红细胞，我们结合使用糖链阵列、生物层析、非规范氨基酸标记和血凝研究来证明EtpA是ETEC血型A特异性凝集素/血凝素的主要成分。重要的是，我们还证明了EtpA与A型血型人肠道上皮细胞上表达的糖链特异地相互作用，并且EtpA介导的细菌-宿主相互作用加速了细菌的黏附和ETEC热不稳定和热稳定毒素的有效传递。总而言之，这些数据提供了对严重ETEC腹泻疾病的复杂分子基础的进一步洞察，这可能为合理设计疫苗以保护高风险人群提供信息。
Enterotoxigenic Escherichia coli (ETEC) infections are highly prevalent in developing countries, where clinical presentations range from asymptomatic colonization to severe cholera-like illness. The molecular basis for these varied presentations, which may involve strain-specific virulence features as well as host factors, has not been elucidated. We demonstrate that, when challenged with ETEC strain H10407, originally isolated from a case of cholera-like illness, blood group A human volunteers developed severe diarrhea more frequently than individuals from other blood groups. Interestingly, a diverse population of ETEC strains, including H10407, secrete the EtpA adhesin molecule. As many bacterial adhesins also agglutinate red blood cells, we combined the use of glycan arrays, biolayer inferometry, and noncanonical amino acid labeling with hemagglutination studies to demonstrate that EtpA is a dominant ETEC blood group A-specific lectin/hemagglutinin. Importantly, we have also shown that EtpA interacts specifically with glycans expressed on intestinal epithelial cells from blood group A individuals and that EtpA-mediated bacterial-host interactions accelerate bacterial adhesion and effective delivery of both the heat-labile and heat-stable toxins of ETEC. Collectively, these data provide additional insight into the complex molecular basis of severe ETEC diarrheal illness that may inform rational design of vaccines to protect those at highest risk.