Allelic variation contributes to bacterial host specificity.
Allelic variation contributes to bacterial host specificity.
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DOI：
10.1038/ncomms9754
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发表时间：
2015-10-30
影响因子：
16.6
通讯作者：
Schifferli DM
中科院分区：
文献类型：
--
作者：
Yue M;Han X;De Masi L;Zhu C;Ma X;Zhang J;Wu R;Schmieder R;Kaushik RS;Fraser GP;Zhao S;McDermott PF;Weill FX;Mainil JG;Arze C;Fricke WF;Edwards RA;Brisson D;Zhang NR;Rankin SC;Schifferli DM
了解调节潜在病原体的跨物种传播和宿主适应的分子参数对于控制新出现的传染病至关重要。虽然微生物致病型的多样性通常与基因的获得或丢失有关，但病理适应性非同义单核苷酸多态性（nsSNPs）的作用尚未得到系统评价。在这里，我们的全基因组分析的核心基因在沙门氏菌肠道血清型鼠伤寒沙门氏菌基因组揭示了高度的等位基因变异的表面暴露的分子，包括粘附素，促进宿主定植。随后对580个独立鼠伤寒杆菌分离株的已知/疑似粘附素进行多项逻辑回归、MultiPhen和Random Forest分析，识别出不同的宿主特异性nsSNP特征。此外，对FimH（1型菌毛粘附素）的宿主相关nsSNP的群体和功能分析突出了关键等位基因残基在体外宿主特异性粘附中的作用。总之，我们的数据提供了第一个具体证据，表明细菌蛋白质等位基因变体之间的功能差异可能有助于对不同宿主的病理适应。 控制传染病的一个关键方面是了解病原体如何跨越宿主物种。在这里，作者进行了沙门氏菌的全基因组分析，并显示出高度的变异，使宿主适应沙门氏菌肠道和全身血清型之间的殖民。
Understanding the molecular parameters that regulate cross-species transmission and host adaptation of potential pathogens is crucial to control emerging infectious disease. Although microbial pathotype diversity is conventionally associated with gene gain or loss, the role of pathoadaptive nonsynonymous single-nucleotide polymorphisms (nsSNPs) has not been systematically evaluated. Here, our genome-wide analysis of core genes within Salmonella enterica serovar Typhimurium genomes reveals a high degree of allelic variation in surface-exposed molecules, including adhesins that promote host colonization. Subsequent multinomial logistic regression, MultiPhen and Random Forest analyses of known/suspected adhesins from 580 independent Typhimurium isolates identifies distinct host-specific nsSNP signatures. Moreover, population and functional analyses of host-associated nsSNPs for FimH, the type 1 fimbrial adhesin, highlights the role of key allelic residues in host-specific adherence in vitro. Together, our data provide the first concrete evidence that functional differences between allelic variants of bacterial proteins likely contribute to pathoadaption to diverse hosts. One of the key aspects for controlling infectious diseases is understanding how pathogens cross host species. Here the authors conduct a genome-wide analysis of Salmonella and show a high degree of variation, enabling host-adapted colonization among Salmonella intestinal and systemic serovars.