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假定ABC转运蛋白的底物结合蛋白SBP2作为卡他莫拉菌的一种新型疫苗抗原。

Substrate binding protein SBP2 of a putative ABC transporter as a novel vaccine antigen of Moraxella catarrhalis.

作者信息

Otsuka Taketo, Kirkham Charmaine, Johnson Antoinette, Jones Megan M, Murphy Timothy F

机构信息

Division of Infectious Diseases, Department of Medicine, University at Buffalo, State University of New York, Buffalo, New York, USA Clinical and Translational Research Center, University at Buffalo, State University of New York, Buffalo, New York, USA.

Clinical and Translational Research Center, University at Buffalo, State University of New York, Buffalo, New York, USA Department of Microbiology and Immunology, University at Buffalo, State University of New York, Buffalo, New York, USA.

出版信息

Infect Immun. 2014 Aug;82(8):3503-12. doi: 10.1128/IAI.01832-14. Epub 2014 Jun 9.

Abstract

Moraxella catarrhalis is a common respiratory tract pathogen that causes otitis media in children and infections in adults with chronic obstructive pulmonary disease. Since the introduction of the pneumococcal conjugate vaccines with/without protein D of nontypeable Haemophilus influenzae, M. catarrhalis has become a high-priority pathogen in otitis media. For the development of antibacterial vaccines and therapies, substrate binding proteins of ATP-binding cassette transporters are important targets. In this study, we identified and characterized a substrate binding protein, SBP2, of M. catarrhalis. Among 30 clinical isolates tested, the sbp2 gene sequence was highly conserved. In 2 different analyses (whole-cell enzyme-linked immunosorbent assay and flow cytometry), polyclonal antibodies raised to recombinant SBP2 demonstrated that SBP2 expresses epitopes on the bacterial surface of the wild type but not the sbp2 mutant. Mice immunized with recombinant SBP2 showed significantly enhanced clearance of M. catarrhalis from the lung compared to that in the control group at both 25-μg and 50-μg doses (P < 0.001). We conclude that SBP2 is a novel, attractive candidate as a vaccine antigen against M. catarrhalis.

摘要

卡他莫拉菌是一种常见的呼吸道病原体,可导致儿童中耳炎以及患有慢性阻塞性肺疾病的成年人感染。自从引入含/不含不可分型流感嗜血杆菌蛋白D的肺炎球菌结合疫苗以来,卡他莫拉菌已成为中耳炎的高优先级病原体。对于抗菌疫苗和疗法的研发而言,ATP结合盒转运体的底物结合蛋白是重要靶点。在本研究中,我们鉴定并表征了卡他莫拉菌的一种底物结合蛋白SBP2。在所检测的30株临床分离株中,sbp2基因序列高度保守。在两种不同分析(全细胞酶联免疫吸附测定和流式细胞术)中,针对重组SBP2产生的多克隆抗体表明,SBP2在野生型细菌表面表达表位,但在sbp2突变体表面不表达。用重组SBP2免疫的小鼠在25μg和50μg剂量下,与对照组相比,肺部卡他莫拉菌的清除率均显著提高(P < 0.001)。我们得出结论,SBP2是一种新型的、有吸引力的抗卡他莫拉菌疫苗抗原候选物。

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