Identification of in vivo-induced bacterial protein antigens during human infection with Salmonella enterica serovar Typhi
Identification of in vivo-induced bacterial protein antigens during human infection with Salmonella enterica serovar Typhi
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DOI：
10.1128/iai.00488-06
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发表时间：
2006-09-01
影响因子：
3.1
通讯作者：
Ryan, Edward T.
中科院分区：
文献类型：
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作者：
Harris, Jason B.;Baresch-Bernal, Andrea;Ryan, Edward T.
我们应用免疫筛选技术，即体内诱导抗原技术 (IVIAT)，来鉴定人类感染伤寒沙门氏菌（伤寒的病因）期间表达的免疫原性细菌蛋白。我们能够对 IVIAT 鉴定的 35 种蛋白质中的 25 种进行功能分类。在这 25 个蛋白中，大多数代表在肠沙门氏菌发病机制中具有已知或潜在作用的蛋白。这些包括与菌毛结构和生物发生、抗菌素耐药性、重金属转运、细菌粘附、胞质外底物运输以及分泌的水解酶有关的蛋白质。剩下的 10 个抗原代表功能未知的蛋白质。在 35 种已鉴定的抗原中，当用来自从未接触过伤寒菌血清型的个体的对照血清进行探测时，有 4 种没有免疫反应性；这四种包括 PagC、TcfB 以及由 STY0860 和 STY3683 编码的两种功能未知的抗原。 PagC 是一种已知在小鼠鼠伤寒沙门氏菌感染体内上调的毒力因子。 TcfB 是伤寒血清型中发现的菌毛操纵子的主要结构亚基，在鼠伤寒血清型生物体中没有同源物。通过检查急性期与恢复期人血清样本中的差异免疫反应性，我们发现伤寒血清型菌血症患者存在特异性抗 PagC 和抗 TcfB 免疫球蛋白 G 反应。 IVIAT 鉴定出的伤寒血清抗原值得进一步评估其对发病机制的贡献，并且它们可能具有诊断、治疗或预防用途。
We applied an immunoscreening technique, in vivo-induced antigen technology (IVIAT), to identify immunogenic bacterial proteins expressed during human infection with Salmonella enterica serovar Typhi, the cause of typhoid fever. We were able to assign a functional classification to 25 of 35 proteins identified by IVIAT. Of these 25, the majority represent proteins with known or potential roles in the pathogenesis of S. enterica. These include proteins implicated in fimbrial structure and biogenesis, antimicrobial resistance, heavy metal transport, bacterial adhesion, and extracytoplasmic substrate trafficking as well as secreted hydrolases. The 10 remaining antigens represent proteins with unknown functions. Of the 35 identified antigens, four had no immunoreactivity when probed with control sera from individuals never exposed to serovar Typhi organisms; these four included PagC, TcfB, and two antigens of unknown function encoded by STY0860 and STY3683. PagC is a virulence factor known to be upregulated in vivo in S. enterica serovar Typhimurium infection of mice. TcfB is the major structural subunit of a fimbrial operon found in serovar Typhi with no homolog in serovar Typhimurium organisms. By examining differential immunoreactivities in acute- versus convalescent-phase human serum samples, we found specific anti-PagC and anti-TcfB immunoglobulin G responses in patients with serovar Typhi bacteremia. Serovar Typhi antigens identified by IVIAT warrant further evaluation for their contributions to pathogenesis, and they may have diagnostic, therapeutic, or preventive uses.