RESUMEN
Shigella species are a group of highly transmissible Gram-negative pathogens. Increasing reports of infection with extensively drug-resistant varieties of this stomach bug has convinced the World Health Organization to prioritize Shigella for novel therapeutic interventions. We herein coupled the whole-genome sequencing of a natural isolate of Shigella flexneri with a pangenome ana-lysis to characterize pathogen genomics within this species, which will provide us with an insight into its existing genomic diversity and highlight the root causes behind the emergence of quick vaccine escape variants. The isolated novel strain of S. flexneri contained ~4,500 protein-coding genes, 57 of which imparted resistance to antibiotics. A comparative pan-genomic ana-lysis revealed genomic variability of ~64%, the shared conservation of core genes in central metabolic processes, and the enrichment of unique/accessory genes in virulence and defense mechanisms that contributed to much of the observed antimicrobial resistance (AMR). A pathway ana-lysis of the core genome mapped 22 genes to 2 antimicrobial resistance pathways, with the bulk coding for multidrug efflux pumps and two component regulatory systems that are considered to work synergistically towards the development of resistance phenotypes. The prospective evolvability of Shigella species as witnessed by the marked difference in genomic content, the strain-specific essentiality of unique/accessory genes, and the inclusion of a potent resistance mechanism within the core genome, strengthens the possibility of novel serotypes emerging in the near future and emphasizes the importance of tracking down genomic diversity in drug/vaccine design and AMR governance.
Asunto(s)
Antibacterianos , Genoma Bacteriano , Genómica , Shigella flexneri , Aguas Residuales , Shigella flexneri/genética , Shigella flexneri/aislamiento & purificación , Shigella flexneri/clasificación , Shigella flexneri/efectos de los fármacos , Genoma Bacteriano/genética , Aguas Residuales/microbiología , Antibacterianos/farmacología , Filogenia , Secuenciación Completa del Genoma , Farmacorresistencia Bacteriana Múltiple/genética , Virulencia/genéticaRESUMEN
The Bacillus subtilis group (Bs group), with Bacillus subtilis as its core species, holds significant research and economic value in various fields, including science, industrial production, food, and pharmaceuticals. However, most studies have been confined to comparative genomics analyses and exploration within individual genomes at the level of species, with few conducted within groups across different species. This study focused on Bacillus subtilis, the model of Gram-positive bacteria, and 14 other species with significant research value, employing comparative pangenomics as well as population enrichment analysis to ascertain the functional enrichment and diversity. Through the quantification of pangenome openness, this work revealed the underlying biological drivers and significant correlation between pangenome openness and various factors, including the distribution of toxin-antitoxin- and integrase-related genes, as well as the number of endonucleases, recombinases, repair system-related genes, prophages, integrases, and transfer mobile elements. Furthermore, the functional enrichment results indicated the potential for secondary metabolite, probiotic, and antibiotic exploration in Bacillus licheniformis, Bacillus paralicheniformis, and Bacillus spizizenii, respectively. In general, this work systematically exposed the quantification of pangenome openness, biological drivers, the pivotal role of genomic instability factors, and mobile elements, providing targeted exploration guidance for the Bs group.
RESUMEN
Graph-based pangenome is gaining more popularity than linear pangenome because it stores more comprehensive information of variations. However, traditional linear genome browser has its own advantages, especially the tremendous resources accumulated historically. With the fast-growing number of individual genomes and their annotations available, the demand for a genome browser to visualize genome annotation for many individuals together with a graph-based pangenome is getting higher and higher. Here we report a new pangenome browser PPanG, a precise pangenome browser enabling nucleotide-level comparison of individual genome annotations together with a graph-based pangenome. Nine rice genomes with annotations were provided by default as potential references, and any individual genome can be selected as the reference. Our pangenome browser provides unprecedented insights on genome variations at different levels from base to gene, and reveals how the structures of a gene could differ for individuals. PPanG can be applied to any species with multiple individual genomes available and it is available at https://cgm.sjtu.edu.cn/PPanG .
Asunto(s)
Genómica , Genómica/métodos , Oryza/genética , Anotación de Secuencia Molecular , Genoma de Planta , Variación Genética , Programas Informáticos , Navegador Web , Bases de Datos Genéticas , Nucleótidos/genética , GenomaRESUMEN
BACKGROUND: Enterococcus faecalis is the most commonly isolated enterococcal species in clinical infection. This bacterium is notorious for its ability to share genetic content within and outside of its species. With this increased proficiency for horizontal gene transfer, tremendous genomic diversity within this species has been identified. Many researchers have hypothesized E. faecalis exhibits niche adaptation to establish infections or colonize various parts of the human body. Here, we hypothesize that E. faecalis strains isolated from the human bladder will carry unique genomic content compared to clinical strains isolated from other sources. RESULTS: This analysis includes comparison of 111 E. faecalis genomes isolated from bladder, urogenital, blood, and fecal samples. Phylogenomic comparison shows no association between isolation source and lineage; however, accessory genome comparison differentiates blood and bladder genomes. Further gene enrichment analysis identifies gene functions, virulence factors, antibiotic resistance genes, and plasmid-associated genes that are enriched or rare in bladder genomes compared to urogenital, blood, and fecal genomes. Using these findings as training data and 682 publicly available genomes as test data, machine learning classifiers successfully distinguished between bladder and non-bladder strains with high accuracy. Genes identified as important for this differentiation were often related to transposable elements and phage, including 3 prophage species found almost exclusively in bladder and urogenital genomes. CONCLUSIONS: E. faecalis strains isolated from the bladder contain unique genomic content when compared to strains isolated from other body sites. This genomic diversity is most likely due to horizontal gene transfer, as evidenced by lack of phylogenomic clustering and enrichment of transposable elements and prophages. Investigation into how these enriched genes influence host-microbe interactions may elucidate gene functions required for successful bladder colonization and disease establishment.