LEE-encoded regulator (Ler) mutants elicit serotype-specific protection, but not cross protection, against attaching and effacing E. coli strains.

LEE-encoded regulator (Ler) mutants elicit serotype-specific protection, but not cross protection, against attaching and effacing E. coli strains.
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LEE 编码的调节因子 (Ler) 突变体会​​引发血清型特异性保护,但不会产生交叉保护,以防止大肠杆菌菌株的附着和消失。

DOI:
10.1016/j.vaccine.2006.10.026
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发表时间:
2007
期刊:
影响因子:
5.5
通讯作者:
Boedeker,EC
Boedeker,EC
中科院分区:
医学3区
文献类型:
--
作者:
Zhu,C;Feng,S;Yang,Z;Davis,K;Rios,H;Kaper,JB;Boedeker,EC

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我们之前表明,用兔致病性大肠杆菌(REPEC)菌株E22(O103:H2)的减毒调节Lee编码调节器(ler)突变体进行单剂量口胃免疫可以保护兔子免受高毒力亲本菌株的致命感染。在当前的研究中,我们评估了用不同血清型的 REPEC ler 突变菌株或表达全系列 ler 上调蛋白的原型菌株 RDEC-1 (O15:H-) 免疫诱导的同源(血清型特异性)和异源(跨血清型)保护程度。因此,我们使用 RDEC-1 构建了一个额外的 ler 突变体,允许用血清型 O15 或 O103 的 ler 突变体进行免疫,然后用相同或不同血清型的强毒力 REPEC 菌株进行攻击。与我们之前的数据一致,当前的研究表明,用 RDEC-1 ler 突变体免疫的兔子可以免受相同血清型的有毒 RDEC-H19A(用产生志贺毒素的噬菌体 H19A 转导的 RDEC-1)的攻击。用RDEC-1或E22衍生ler突变体免疫的兔子表现出针对表达O抗原的相应完整细菌细胞的血清抗体滴度显着增加,但针对LEE编码蛋白的血清抗体滴度没有显着增加。然而,用 E22 或 RDEC-1 的 ler 突变体进行免疫未能保护兔子免受属于不同血清型的有毒生物体的感染。相比之下,用原型 RDEC-1 免疫的兔子受到交叉保护,免受异源 E22 菌株的攻击,如正常体重增加所示,并且没有疾病的临床症状或特征性附着和消失 (A/E) 损伤。 RDEC-1 免疫诱导 LEE 编码蛋白的血清 IgG 滴度显着升高。因此,我们证明了 REPEC ler 突变体诱导的同源保护和 RDEC-1 诱导的异源保护。观察到的对 LEE 编码蛋白的免疫应答升高与针对异源毒力 REPEC 菌株攻击的保护之间的相关性表明,血清型非特异性交叉保护需要 LEE 编码毒力因子的表达和抗体的诱导。
We previously showed that single dose orogastric immunization with an attenuated regulatory Lee-encoded regulator (ler) mutant of the rabbit enteropathogenic Escherichia coli (REPEC) strain E22 (O103:H2) protected rabbits from fatal infection with the highly virulent parent strain. In the current study we assessed the degree of homologous (serotype-specific) and heterologous (cross-serotype) protection induced by immunization with REPEC ler mutant strains of differing serotypes, or with a prototype strain RDEC-1 (O15:H-) which expresses a full array of ler up-regulated proteins. We constructed an additional ler mutant using RDEC-1 thus, permitting immunization with a ler mutant of either serotype, O15 or O103, followed by challenge with a virulent REPEC strain of the same or different serotypes. Consistent with our previous data, the current study demonstrated that rabbits immunized with a RDEC-1 ler mutant were protected from challenge with virulent RDEC-H19A (RDEC-1 transduced with Shiga toxin-producing phage H19A) of the same serotype. Rabbits immunized with RDEC-1 or E22 derivative ler mutants demonstrated significant increase in serum antibody titers to the respective whole bacterial cells expressing O antigen but not to the LEE-encoded proteins. However, immunization with the ler mutants of either E22 or RDEC-1 failed to protect rabbits from infections with virulent organisms belonging to different serotypes. In contrast, rabbits immunized with the prototype RDEC-1 were cross protected against challenge with the heterologous E22 strain as shown by normal weight gain, and the absence of clinical signs of disease or characteristic attaching and effacing (A/E) lesions. Immunization with RDEC-1 induced significantly elevated serum IgG titers to LEE-encoded proteins. We thus, demonstrated homologous protection induced by the REPEC ler mutants and heterologous protection by RDEC-1. The observed correlation between elevated immune responses to the LEE-encoded proteins and the protection against challenge with heterologous virulent REPEC strain suggests that serotype-non-specific cross protection requires the expression of, and induction of antibody to, LEE-encoded virulence factors.
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