Comparative Pathogenomics of Escherichia coli: Polyvalent Vaccine Target Identification through Virulome Analysis.
Comparative Pathogenomics of Escherichia coli: Polyvalent Vaccine Target Identification through Virulome Analysis.
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DOI：
10.1128/iai.00115-21
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发表时间：
2021-07-15
影响因子：
3.1
通讯作者：
Maresso AM
中科院分区：
文献类型：
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作者：
Clark JR;Maresso AM
细菌病原体的比较基因组学有助于揭示潜在的毒力因子。大肠杆菌是世界范围内人类发病率和死亡率的重要原因，但也可以作为共生菌存在于人类胃肠道中。由于有许多测序的基因组，它已经成为比较基因组研究的模式生物，以了解遗传含量和潜在毒力之间的联系。然而，到目前为止，还没有对其完整的“病毒组”进行全面分析，以确定疫苗开发的通用或病毒型特异性靶标。在这里，我们描述了107个具有完整序列特征的致病和非致病大肠杆菌菌株的病毒型数据库的构建，并对其进行了主要毒力因子(VFS)的注释。这些数据与病毒型、种子组和序列类型的模式进行了交叉参考，结果与NCBI RefSeq数据库中的所有1348条完整的大肠杆菌染色体进行了验证。我们的结果表明，系统群驱动了许多“致病相关”的VF，而ExPEC相关的VF主要发现在B2/D/F/G系统发生支系中，这表明这些系统群更适合感染人类宿主。最后，我们利用这些信息提出了针对肠外菌株的多价疫苗靶点，针对关键的侵袭策略，包括免疫逃避(第2组胶囊)、铁获取(FyuA、Iuta和Sit)、粘附性(Sinh、Afa、Pap、SFA和Iha)和毒素(USP、Sat、VAT、CDT、Cnf1和HlyA)。虽然之前已经提出了许多这样的靶点，但这项工作是第一次检查它们的致病类型和系统群分布，以及它们如何被一起作为靶点来预防疾病。
Comparative genomics of bacterial pathogens has been useful for revealing potential virulence factors. Escherichia coli is a significant cause of human morbidity and mortality worldwide but can also exist as a commensal in the human gastrointestinal tract. With many sequenced genomes, it has served as a model organism for comparative genomic studies to understand the link between genetic content and potential for virulence. To date, however, no comprehensive analysis of its complete “virulome” has been performed for the purpose of identifying universal or pathotype-specific targets for vaccine development. Here, we describe the construction of a pathotype database of 107 well-characterized completely sequenced pathogenic and nonpathogenic E. coli strains, which we annotated for major virulence factors (VFs). The data are cross referenced for patterns against pathotype, phylogroup, and sequence type, and the results were verified against all 1,348 complete E. coli chromosomes in the NCBI RefSeq database. Our results demonstrate that phylogroup drives many of the “pathotype-associated” VFs, and ExPEC-associated VFs are found predominantly within the B2/D/F/G phylogenetic clade, suggesting that these phylogroups are better adapted to infect human hosts. Finally, we used this information to propose polyvalent vaccine targets with specificity toward extraintestinal strains, targeting key invasive strategies, including immune evasion (group 2 capsule), iron acquisition (FyuA, IutA, and Sit), adherence (SinH, Afa, Pap, Sfa, and Iha), and toxins (Usp, Sat, Vat, Cdt, Cnf1, and HlyA). While many of these targets have been proposed before, this work is the first to examine their pathotype and phylogroup distribution and how they may be targeted together to prevent disease.
影响因子：
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作者：
Segura A;Auffret P;Klopp C;Bertin Y;Forano E
通讯作者：
Forano E