Pangenome evaluation of gene essentiality in Streptococcus pyogenes

被引:2
|
作者
Jespersen, Magnus G. [1 ]
Hayes, Andrew J. [1 ]
Tong, Steven Y. C. [2 ,3 ]
Davies, Mark R. [1 ]
机构
[1] Univ Melbourne, Peter Doherty Inst Infect & Immun, Dept Microbiol & Immunol, Melbourne, Australia
[2] Univ Melbourne, Peter Doherty Inst Infect & Immun, Dept Infect Dis, Melbourne, Australia
[3] Royal Melbourne Hosp, Victorian Infect Dis Serv, Peter Doherty Inst Infect & Immun, Melbourne, Australia
来源
MICROBIOLOGY SPECTRUM | 2024年 / 12卷 / 08期
关键词
genomics; Streptococcus pyogenes; gene disruption; pangenome; GROUP-A STREPTOCOCCUS; MUTANS; FFH;
D O I
10.1128/spectrum.03240-23
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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 Streptococcus pyogenes, yet challenges exist in comparing results across studies conducted in different genetic backgrounds and conditions. To advance genotype to phenotype inferences across different S. pyogenes strains, we built a pangenome database of 249 S. pyogenes reference genomes. We systematically re-analyzed publicly available transposon sequencing datasets from S. pyogenes using a transposon sequencing-specific analysis pipeline, Transit. Across four genetic backgrounds and nine phenotypic conditions, 355 genes were essential for survival, corresponding to similar 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 S. pyogenes genotypes were defined, with an increased number of essential operons detected under in vivo 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 S. pyogenes biology. IMPORTANCE Streptococcus pyogenes 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 S. pyogenes. To this end we systematically reanalyzed transposon sequencing studies in S. pyogenes using transposon sequencing-specific methods, integrating them into an extendible meta-analysis framework. This provides a repository of gene essentiality in S. pyogenes which was used to highlight specific genes of interest and for the community to guide future phenotypic studies.
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页数:16
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