Pangenome evaluation of gene essentiality in .

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.