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首页> 外文期刊>BMC Genomics >Steps toward broad-spectrum therapeutics: discovering virulence-associated genes present in diverse human pathogens
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Steps toward broad-spectrum therapeutics: discovering virulence-associated genes present in diverse human pathogens

机译：迈向广谱疗法的步骤：发现多种人类病原体中存在的毒力相关基因

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Background New and improved antimicrobial countermeasures are urgently needed to counteract increased resistance to existing antimicrobial treatments and to combat currently untreatable or new emerging infectious diseases. We demonstrate that computational comparative genomics, together with experimental screening, can identify potential generic (i.e., conserved across multiple pathogen species) and novel virulence-associated genes that may serve as targets for broad-spectrum countermeasures. Results Using phylogenetic profiles of protein clusters from completed microbial genome sequences, we identified seventeen protein candidates that are common to diverse human pathogens and absent or uncommon in non-pathogens. Mutants of 13 of these candidates were successfully generated in Yersinia pseudotuberculosis and the potential role of the proteins in virulence was assayed in an animal model. Six candidate proteins are suggested to be involved in the virulence of Y. pseudotuberculosis, none of which have previously been implicated in the virulence of Y. pseudotuberculosis and three have no record of involvement in the virulence of any bacteria. Conclusion This work demonstrates a strategy for the identification of potential virulence factors that are conserved across a number of human pathogenic bacterial species, confirming the usefulness of this tool.
机译：背景技术迫切需要新的和改进的抗微生物对策，以抵消对现有抗微生物治疗的增加的耐药性并与当前无法治愈的或新出现的传染病作斗争。我们证明了计算比较基因组学以及实验筛选可以确定潜在的通用（即跨多种病原体保守）和新的与毒力相关的基因，它们可以作为广谱对策的目标。结果利用完整微生物基因组序列中蛋白质簇的系统发育谱，我们鉴定了十七种蛋白质候选物，这些候选物是多种人类病原体共有的，而在非病原体中则不存在或罕见。这些候选物中的13个突变体已在假结核耶尔森氏菌中成功产生，并在动物模型中测定了蛋白质在毒性中的潜在作用。建议有六种候选蛋白与假结核耶尔森氏菌的毒力有关，以前没有一种蛋白与假结核耶尔森氏菌的毒力有关，还有三种没有涉及任何细菌毒力的记录。结论这项工作证明了一种策略，可用于识别在许多人类致病细菌物种中保守的潜在毒力因子，从而证实了该工具的实用性。

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