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靶向IV型分泌系统蛋白以对抗多重耐药革兰氏阳性病原体。

Targeting Type IV Secretion System Proteins to Combat Multidrug-Resistant Gram-positive Pathogens.

作者信息

Laverde Diana, Probst Ines, Romero-Saavedra Felipe, Kropec Andrea, Wobser Dominique, Keller Walter, Grohmann Elisabeth, Huebner Johannes

机构信息

Division of Pediatric Infectious Diseases, Dr. von Hauner Children's Hospital, Ludwig Maximilians University, Munich.

Division of Infectious Diseases, Department of Medicine, University Medical Center Freiburg.

出版信息

J Infect Dis. 2017 Jun 15;215(12):1836-1845. doi: 10.1093/infdis/jix227.

Abstract

For many gram-positive pathogens, conjugative plasmid transfer is an important means of spreading antibiotic resistance . Therefore, the search for alternative treatments to fight and prevent infections caused by these bacteria has become of major interest. In the present study, we evaluated the protein TraM, from the conjugative plasmid pIP501, as a potential vaccine candidate. Anti-TraM antiserum mediated in vitro opsonophagocytic killing of the strain harboring the pIP501 plasmid and also proved to be cross-reactive against other clinically relevant enterococcal and staphylococcal strains. Specificity of antibodies toward TraM was confirmed by results of an opsonophagocytic inhibition assay and Western blot. In addition, conjugative transfer experiments proved that TraM is essential for the transfer of pIP501. Finally, immunization with either TraM or anti-TraM antiserum reduced significantly the colony counts in mice livers, demonstrating that TraM is a promising vaccine candidate against enterococci and other gram-positive pathogens.

摘要

对于许多革兰氏阳性病原体而言,接合性质粒转移是传播抗生素耐药性的重要途径。因此,寻找对抗和预防这些细菌引起的感染的替代治疗方法已成为主要研究热点。在本研究中,我们评估了来自接合性质粒pIP501的蛋白质TraM作为潜在疫苗候选物的可能性。抗TraM抗血清介导了对携带pIP501质粒菌株的体外调理吞噬杀伤作用,并且还被证明对其他临床相关的肠球菌和葡萄球菌菌株具有交叉反应性。调理吞噬抑制试验和蛋白质印迹结果证实了抗体对TraM的特异性。此外,接合转移实验证明TraM对于pIP501的转移至关重要。最后,用TraM或抗TraM抗血清进行免疫显著降低了小鼠肝脏中的菌落计数,表明TraM是一种有前景的抗肠球菌和其他革兰氏阳性病原体的疫苗候选物。

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