ROLE OF THE EAEA GENE IN EXPERIMENTAL ENTEROPATHOGENIC ESCHERICHIA-COLI INFECTION
ROLE OF THE EAEA GENE IN EXPERIMENTAL ENTEROPATHOGENIC ESCHERICHIA-COLI INFECTION
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DOI：
10.1172/jci116717
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发表时间：
1993-09-01
影响因子：
15.9
通讯作者：
LEVINE, MM
中科院分区：
文献类型：
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作者：
DONNENBERG, MS;TACKET, CO;LEVINE, MM
肠致病性大肠杆菌（EPEC）感染是发展中国家婴儿腹泻的主要原因。在组织培养中，EPEC与上皮细胞密切附着所必需的基因eaeA被描述。我们进行了一项随机双盲研究，以确定eaeA基因在人EPEC感染中的作用。11名成年志愿者摄入了2 × 10（10）个集落形成单位的0127:H6 EPEC菌株E2348/69，同样数量的志愿者接受了相同剂量的由E2348/69构建的等基因eaeA缺失突变体。研究人员监测志愿者是否出现腹泻、发烧、全身和胃肠道不适。所有11名接受E2348/69治疗的志愿者和11名接受突变体治疗的志愿者中有4人出现腹泻（P = 0.002）。发热在野生型感染人群中更为常见（P = 0.024）。突变体受体的粪便量较低。所有志愿者血清均转化为E2348/69 LPS，但突变株受体血清IgG和IgA的几何平均峰值滴度低于野生型受体。在6名E2348/69受体和5/6突变体受体的空肠液中检测到抗LPS的IgA。本研究明确指定eaeA作为EPEC毒力基因的作用，但在突变体受体中看到的残余腹泻表明涉及其他因素。
Enteropathogenic Escherichia coli (EPEC) infections are a leading cause of infant diarrhea in developing countries. Recently eaeA, a gene necessary for the characteristic intimate attachment of EPEC to epithelial cells in tissue culture, was described. We conducted a randomized, double-blind study to determine the role of the eaeA gene in human EPEC infection. 11 adult volunteers ingested 2 X 10(10) colony-forming units of 0127:H6 EPEC strain E2348/69, and an equal number received the same dose of an isogenic eaeA deletion mutant constructed from E2348/69. Volunteers were monitored for the development of diarrhea, fever, and systemic and gastrointestinal complaints. Diarrhea developed in all 11 volunteers who received E2348/69 and in 4 of 11 who received the mutant (P = 0.002). Fever was more common in recipients of the wild-type strain (P = 0.024). Stool volumes were lower in recipients of the mutant. All volunteers seroconverted to E2348/69 LPS, but the geometric mean peak titers of serum IgG and IgA in recipients of the mutant were lower than those of recipients of the wild-type strain. IgA against LPS was detected in the jejunal fluid of six of six recipients of E2348/69 and 5/6 recipients of the mutant. This study unambiguously assigns a role for eaeA as an EPEC virulence gene, but the residual diarrhea seen in recipients of the mutant indicates that other factors are involved.