Characterization of Anti-Salmonella enterica Serotype Typhi Antibody Responses in Bacteremic Bangladeshi Patients by an Immunoaffinity Proteomics-Based Technology
Characterization of Anti-Salmonella enterica Serotype Typhi Antibody Responses in Bacteremic Bangladeshi Patients by an Immunoaffinity Proteomics-Based Technology
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DOI：
10.1128/cvi.00104-10
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发表时间：
2010-08-01
影响因子：
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通讯作者：
Ryan, Edward T.
中科院分区：
文献类型：
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作者：
Charles, Richelle C.;Sheikh, Alaullah;Ryan, Edward T.
伤寒沙门氏菌血清型是伤寒的病因，也是一种人类限制性病原体。目前可用的伤寒疫苗提供50%至90%的保护2至5年，和可用的实用诊断测定，以确定个人与伤寒缺乏敏感性和/或特异性。鉴定免疫原性S.在人类感染期间表达的伤寒抗原可能导致改进的诊断测定和疫苗。在这里，我们描述了一种基于免疫亲和蛋白质组学的平台技术（IPT），该技术涉及使用从S菌血症患者中回收的IgG、IgM或伊加抗体组分。伤寒捕获S。伤寒蛋白随后通过质谱鉴定。该筛选工具鉴定被来自感染宿主的抗体识别的免疫原性蛋白。利用该技术和S.在孟加拉国伤寒菌血症中，我们鉴定了57个蛋白。伤寒，包括已知具有免疫原性的蛋白质（PagC、HlyE、OmpA和GroEL）和存在于人限制性血清型S中的许多蛋白质。伤寒和沙门氏菌。甲型副伤寒，但很少发现在更广泛的宿主范围沙门氏菌属。(HlyE、CdtB、PltA和STY 1364）。我们将鉴定的蛋白质分为许多主要的组，包括那些参与能量代谢、蛋白质合成、铁稳态、生物合成和代谢功能的蛋白质，以及那些预测定位于外膜的蛋白质。我们评估了S.在临床表现时，在患者中检测到抗HlyE应答，但在对照中未检测到。这些发现可以帮助开发改进的诊断测定。
Salmonella enterica serotype Typhi is the cause of typhoid fever and a human-restricted pathogen. Currently available typhoid vaccines provide 50 to 90% protection for 2 to 5 years, and available practical diagnostic assays to identify individuals with typhoid fever lack sensitivity and/or specificity. Identifying immunogenic S. Typhi antigens expressed during human infection could lead to improved diagnostic assays and vaccines. Here we describe a platform immunoaffinity proteomics-based technology (IPT) that involves the use of columns charged with IgG, IgM, or IgA antibody fractions recovered from humans bacteremic with S. Typhi to capture S. Typhi proteins that were subsequently identified by mass spectrometry. This screening tool identifies immunogenic proteins recognized by antibodies from infected hosts. Using this technology and the plasma of patients with S. Typhi bacteremia in Bangladesh, we identified 57 proteins of S. Typhi, including proteins known to be immunogenic (PagC, HlyE, OmpA, and GroEL) and a number of proteins present in the human-restricted serotypes S. Typhi and S. Paratyphi A but rarely found in broader-host-range Salmonella spp. (HlyE, CdtB, PltA, and STY1364). We categorized identified proteins into a number of major groupings, including those involved in energy metabolism, protein synthesis, iron homeostasis, and biosynthetic and metabolic functions and those predicted to localize to the outer membrane. We assessed systemic and mucosal anti-HlyE responses in S. Typhi-infected patients and detected anti-HlyE responses at the time of clinical presentation in patients but not in controls. These findings could assist in the development of improved diagnostic assays.