VARIABILITY OF NEUTROPHIL-ACTIVATING PROTEIN AMONG HELICOBACTER PYLORI STRAINS

C. Calado
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Abstract

The Helicobacter pylori neutrophil activating protein (NAP) presents relevant inflammatory and immunomodulatory activity and has consequently been explored as a diagnosis and therapeutic target. In the present work, nap gene sequences, retrieved from H. pylori isolated world-wide, were analyzed, a high genetic diversity (with 88% of alleles) being observed in accordance with other virulence factors. The phylogenetic analysis did not reveal the separation of strains per geographical region according to a bacterial panmictic population. When compared to other genes of virulence factors of H. pylori, such as the vacuolating cytotoxin A (vacA), nap presents slightly lower genetic variability, concerning the number of alleles and polymorphic sites, pointing to a possible lower pressure of the host immune system. The nap genetic diversity is associated to a high proportion of synonymous substitutions in relation to non-synonymous substitutions, pointing to equilibrium between the need for antigenic diversity as a mechanism to escape the host immune system and the maintenance of the proteins function. All this information could be put to good use when planning the NAP application as a therapeutic or diagnostic target.
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幽门螺杆菌菌株间中性粒细胞活化蛋白的变异
幽门螺杆菌中性粒细胞激活蛋白(NAP)具有相关的炎症和免疫调节活性,因此已被探索作为诊断和治疗靶点。在本工作中,我们分析了从世界各地分离的幽门螺杆菌中检索到的nap基因序列,发现其具有很高的遗传多样性(88%的等位基因),与其他毒力因素一致。系统发育分析并没有显示菌株在每个地理区域的分离,根据一个细菌泛菌群。与幽门螺杆菌毒力因子的其他基因(如空泡细胞毒素A (vacA))相比,nap在等位基因数量和多态性位点方面表现出略低的遗传变异性,表明宿主免疫系统的压力可能较低。与非同义取代相比,nap遗传多样性与同义取代的高比例相关,这表明抗原多样性作为逃避宿主免疫系统的机制的需求与蛋白质功能的维持之间存在平衡。当计划NAP应用程序作为治疗或诊断目标时,所有这些信息都可以很好地使用。
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