Jespersen Magnus G, Hayes Andrew J, Tong Steven Y C, Davies Mark R
Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
Department of Infectious Diseases, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Australia.
Microbiol Spectr. 2024 Aug 6;12(8):e0324023. doi: 10.1128/spectrum.03240-23. Epub 2024 Jul 16.
Bacterial species often consist of strains with variable gene content, collectively referred to as the pangenome. Variations in the genetic makeup of strains can alter bacterial physiology and fitness. To define biologically relevant genes of a genome, genome-wide transposon mutant libraries have been used to identify genes essential for survival or virulence in a given strain. Such phenotypic studies have been conducted in four different genotypes of the human pathogen , yet challenges exist in comparing results across studies conducted in different genetic backgrounds and conditions. To advance genotype to phenotype inferences across different strains, we built a pangenome database of 249 . reference genomes. We systematically re-analyzed publicly available transposon sequencing datasets from using a transposon sequencing-specific analysis pipeline, Transit. Across four genetic backgrounds and nine phenotypic conditions, 355 genes were essential for survival, corresponding to ~24% of the core genome. Clusters of Orthologous Genes (COG) categories related to coenzyme and lipid transport and growth functions were overrepresented as essential. Finally, essential operons across genotypes were defined, with an increased number of essential operons detected under conditions. This study provides an extendible database to which new studies can be added, and a searchable html-based resource to direct future investigations into biology.IMPORTANCE is a human-adapted pathogen occupying restricted ecological niches. Understanding the essentiality of genes across different strains and experimental conditions is important to direct research questions and efforts to prevent the large burden of disease caused by . To this end we systematically reanalyzed transposon sequencing studies in using transposon sequencing-specific methods, integrating them into an extendible meta-analysis framework. This provides a repository of gene essentiality in which was used to highlight specific genes of interest and for the community to guide future phenotypic studies.
细菌物种通常由基因内容可变的菌株组成，这些菌株统称为泛基因组。菌株基因组成的变化会改变细菌的生理特性和适应性。为了定义基因组中具有生物学相关性的基因，全基因组转座子突变文库已被用于识别特定菌株中生存或毒力所必需的基因。此类表型研究已在人类病原体的四种不同基因型中进行，但在比较不同遗传背景和条件下进行的研究结果时仍存在挑战。为了推进不同菌株从基因型到表型的推断，我们构建了一个包含249个参考基因组的泛基因组数据库。我们使用转座子测序特异性分析流程Transit，系统地重新分析了来自[具体来源未给出]的公开可用转座子测序数据集。在四种遗传背景和九种表型条件下，355个基因对生存至关重要，约占核心基因组的24%。与辅酶和脂质转运以及生长功能相关的直系同源基因簇（COG）类别作为必需基因被过度代表。最后，定义了不同基因型中的必需操纵子，在[具体条件未给出]条件下检测到的必需操纵子数量增加。这项研究提供了一个可扩展的数据库，新的研究可以添加到该数据库中，还提供了一个基于网页的可搜索资源，以指导未来对[具体细菌名称未给出]生物学的研究。重要性：[具体细菌名称未给出]是一种适应人类的病原体，占据有限的生态位。了解不同菌株和实验条件下基因的必需性对于指导研究问题以及预防由[具体细菌名称未给出]引起的巨大疾病负担的努力非常重要。为此，我们使用转座子测序特异性方法系统地重新分析了[具体细菌名称未给出]的转座子测序研究，并将它们整合到一个可扩展的荟萃分析框架中。这提供了一个[具体细菌名称未给出]基因必需性的储存库，该储存库用于突出特定的感兴趣基因，并为该领域指导未来的表型研究。
