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粘附素等位基因在宿主嗜性中的协同作用。

Cooperation of Adhesin Alleles in -Host Tropism.

作者信息

De Masi Leon, Yue Min, Hu Changmin, Rakov Alexey V, Rankin Shelley C, Schifferli Dieter M

机构信息

Department of Pathobiology, University of Pennsylvania, School of Veterinary Medicine, Philadelphia, Pennsylvania, USA.

出版信息

mSphere. 2017 Mar 8;2(2). doi: 10.1128/mSphere.00066-17. eCollection 2017 Mar-Apr.

Abstract

Allelic combinations and host specificities for three fimbrial adhesins, FimH, BcfD, and StfH, were compared for 262 strains of serovar Newport, a frequent human and livestock pathogen. Like FimH, BcfD had two major alleles (designated A and B), whereas StfH had two allelic groups, each with two alleles (subgroup A1 and A2 and subgroup B1 and B2). The most prevalent combinations of FimH/BcfD/StfH alleles in . Newport were A/A/A1 and B/B/B1. The former set was most frequently found in bovine and porcine strains, whereas the latter combination was most frequently found in environmental and human isolates. Bacteria genetically engineered to express Fim, Bcf, or Stf fimbriae on their surface were tested with the different alleles for binding to human, porcine, and bovine intestinal epithelial cells. The major allelic combinations with bovine and porcine strains (A/A/A1) or with human isolates (B/B/B1) provided at least two alleles capable of binding significantly better than the other alleles to an intestinal epithelial cell line from the respective host(s). However, each combination of alleles kept at least one allele mediating binding to an intestinal epithelial cell from another host. These findings indicated that allelic variation in multiple adhesins of . Newport contributes to bacterial adaptation to certain preferential hosts without losing the capacity to maintain a broad host range. remains a leading foodborne bacterial pathogen in the United States; infected livestock serve often as the source of contaminated food products. A study estimated that over a billion gastroenteritis cases and up to 33 million typhoid cases occur annually worldwide, with 3.5 million deaths. Although many strains with a broad host range present preferential associations with certain host species, it is not clear what determines the various levels of host adaptation. Here, causal properties of host associations were determined with allelic variants of three colonization factors of serovar Newport, a most frequent zoonotic serovar. This is the first study that related not only individual but also a small group of host-associated gene variants with functional properties that cooperate to determine the level of host-adapted virulence. The detected associations should help to identify sources of infections in both humans and animals.

摘要

对262株纽波特血清型菌株(一种常见的人类和家畜病原体)的三种菌毛粘附素FimH、BcfD和StfH的等位基因组合及宿主特异性进行了比较。与FimH一样,BcfD有两个主要等位基因(命名为A和B),而StfH有两个等位基因组,每组各有两个等位基因(A1和A2亚组以及B1和B2亚组)。纽波特血清型中FimH/BcfD/StfH等位基因最常见的组合是A/A/A1和B/B/B1。前一组在牛和猪菌株中最常见,而后一种组合在环境分离株和人类分离株中最常见。对经基因工程改造在其表面表达Fim、Bcf或Stf菌毛的细菌,用不同等位基因检测其与人、猪和牛肠道上皮细胞的结合情况。与牛和猪菌株相关的主要等位基因组合(A/A/A1)或与人类分离株相关的组合(B/B/B1)提供了至少两个等位基因,它们与各自宿主的肠道上皮细胞系结合的能力明显优于其他等位基因。然而,每种等位基因组合都保留了至少一个介导与另一宿主肠道上皮细胞结合的等位基因。这些发现表明,纽波特血清型多种粘附素的等位基因变异有助于细菌适应某些优先宿主,同时又不会丧失维持广泛宿主范围的能力。在美国,纽波特血清型仍然是主要的食源性病原体;受感染的家畜常常是受污染食品的来源。一项研究估计,全球每年发生超过10亿例肠胃炎病例和多达3300万例伤寒病例,其中有350万人死亡。虽然许多宿主范围广泛的菌株与某些宿主物种存在优先关联,但尚不清楚是什么决定了宿主适应的不同水平。在这里,利用纽波特血清型(一种最常见的人畜共患病血清型)的三种定植因子的等位基因变体确定了宿主关联的因果特性。这是第一项不仅将单个而且将一小群与宿主相关的基因变体与协同决定宿主适应毒力水平的功能特性联系起来的研究。检测到的关联应有助于识别人类和动物感染的来源。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f30/5343171/deb5c9f7e884/sph0021722500001.jpg

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