- The pan-genome of Treponema pallidum reveals differences in genome plasticity between subspecies related to venereal and non-venereal syphilis. - Background: Spirochetal organisms of the Treponema genus are responsible for causing Treponematoses.. - Treponema pallidum subsp. - pallidum strains isolated from different parts of the world and a diverse range of hosts were comparatively analysed using pan-genomic strategy. - Phylogenomic, pan-genomic, core genomic and singleton analysis disclosed the close connection among all strains of the pathogen T. - pallidum , its clonal behaviour and showed increases in the sizes of the pan-genome. - Based on the genome plasticity analysis of the subsets containing the subspecies T pallidum subsp. - pertenue , we found differences in the presence/absence of pathogenicity islands (PAIs) and genomic islands (GIs) on subsp.-based study.. - Keywords: Pan-genome, Core genome, Singletons, Treponema pallidum , Syphilis. - 2020 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0. - Full list of author information is available at the end of the article Jaiswal et al. - Spirochetal organisms of the Treponema genus are re- sponsible for causing Treponematoses. - Primarily, the pathogenic treponemes can be classified based on the clinical symptoms of the re- spective disease they cause. - Treponema pallidum subsp.. - Treponema pallidum is a Gram-negative, motile, spirochete human pathogen. - Syphilis chancres may go un- noticed primarily due to their well-documented painless nature and if they are present in those parts of the body that are difficult to visualize (e.g. - some of the responsibility can be attributed to the difficulty in the diagnosis of syphilis and treatment, and lack of access or use of prenatal screening programs [15]. - A new and emerging methodology to get deep insight of the genome of a species or genus is the pan-genomics approach, which was introduced by Tette- lin and collaborators in 2005 working with Streptococcus agalactiae [16]. - the shared genome, which contains only the genes shared between two or more strains, which are not present in all strains of the dataset. - phagedenis and its biotypes Reiter and Kazan) was less than 5% identical, but was indistinguishable from DNA of the yaws spiro- chete T. - This study led to the re- classification of the agents of endemic syphilis, venereal syphilis and yaws as T. - endemicum, Treponema pallidum subsp. - found in any member of the species. - Phylogenomics study of Treponema pallidum strains The phylogenomics relationships between T. - The subspecies responsible for non-venereal syphilis is Treponema pallidum subsp. - endemicum) was positioned between the clusters of Treponema pallidum subsp. - Pertenue and venereal syphilis (Treponema pallidum subsp. - similar to each other and many of the venereal isolates are 100% similar to each other, but the two groups show some difference (Additional file 1: Figure S2). - pal- lidum subsp., compared with the isolates other than genital, anal or Neurosyphilitic samples, which showed similarities ranging from 97 to 100%.. - The Pan-genome, Core genome and singletons of Treponema pallidum. - The main goal of the pan-genome is the comparison of different strains of the same species or even genus at the genomic level. - The core genome and singletons of the complete data- set and all the subsets of T. - pallidum were calculated by the least-squares fit of the exponential regression decay to the mean values, as represented by the formula n = k * exp[―x/τ. - The resulting core genome of the complete dataset (Pan All), the subsets Pan Subsp_pallidum and Pan Subsp_perte- nue, have the following tg(θ) values, respectively. - Concerning the Singletons of the complete dataset (Pan All) and the subsets Pan Subsp_. - Accord- ing to the least-squares fit of the exponential regression decay, the tg(θ) represents the point where the curve sta- bilizes, which may be translated to the number of genes in the core genome after stabilization and the number of singletons that will be added to the pan-genome for each newly sequenced genome. - Considering this rule, the core genome of the subset Subsp_pertenue have higher num- ber of core genes (1038-number of core genes) after stabilization, whereas, the complete dataset haS the smallest number of core genes (318-number of core genes). - The core genes of the complete dataset, the subsets Pan Subsp_pallidum and Pan Subsp_pertenue, of T. - Moreover, the majority of the core genome of all the strains were classified as “poorly charac- terized” (Additional file 1: Table S2A-C).. - Detection of PAIs in the Treponema pallidum genome The presence of pathogenicity islands (PAIs) is generally related to evolution in a different genomic environment [22]. - Some of the other strains from the representing cluster of the den- dogram were also used for the circular genome visualization. - 1 Phylogenomic tree analysis of 53 Strains of Treponema pallidum. - Non-venereal Treponema pallidum strains are present in same clade . - The shapes (circle and triangle) next to the name of the strain indicate the subset of strains used for Pangenome analysis according to the color of the legend respectively. - When compared to each other, we found high similarity of the genes in all the subsp. - pertenue and endemicum (Non- venereal subsp.) were similar to the PAIs 1 and PAIs 4 of subsp.. - pertenue and endemicum (Non- venereal subsp.) were not present in any of the GIs or PAIs of subsp. - pallidum were not present in any of the GIs or PAIs of subsp. - as a result, we found that the genes of some GIs which are present in the GI2 and GI4 in pallidum subspecies and are not reported in any of GIs of the subspecies endemi- cum and pertenue (Table 3). - Most of the genes present in GI2 and GI4 of pallidum subspecies are hypothetical genes but some genes are chemotaxis protein (CheA). - In the last few years, T. - As demonstrated by the widespread clinical manifestations related to syphilis infections, Treponema pallidum subsp. - Though, the understanding of the mechanisms responsible for the widespread distribution capability of T. - Scratching or rubbing these damaged parts of the body can facilitate the lesions spread across the body [28, 29]. - pallidum gives us better understanding of the biology involving its interaction with its hosts. - Acyl carrier protein (ACP) synthase (AcpS) catalyzes the transfer of the 4 ′ -phosphopan- tetheine moiety from coenzyme A (CoA) onto a serine residue of apo-ACP, to convert apo-ACP to the func- tional holo-ACP. - It might be because of the variation in expression of different Tpr proteins in the syphilis spirochete, Treponema pallidum subsp. - A 12- membered protein family Treponema pallidum repeat (tpr) has been identified in T. - pallidum‘s has the ability to cape its surface with host serum pro- teins or mucopolysaccharides to dodge immune re- sponse and immunosuppression of the host triggered by syphilis infection [38]. - pallidum could be phagocytized in the presence of opsonic antibody, antibody targets must be present on the surface of the bacterium. - During experimental infection, these V regions are the main targets of the host humoral immune response [38].. - 6 Circular genomic representation of islands (PAIs and GIs) in the genomes of T. - Antigenic variation of the TprK antigen has been ac- knowledged to explain the persistence of T. - pallidum in the host.. - [47] has recognized an im- proved number of variants within these seven V regions of the tprK gene in the samples of secondary syphilis. - A 3-bp changing pattern was observed in the sequences within each V region of the protein. - within each V region of the primary and secondary syph- ilis samples, particularly the amino acid sequences IASDGGAIKH and IASEDGSAGNLKH in V1 region.. - 2019, tpr genes responsible for the adaptive evolution of the patho- gen [48].. - 7 Circular genomic representation of islands (PAIs and GIs) in the genomes of T. - 8 Circular genomic representation of islands (PAIs and GIs) in the genomes of T. - and regulation of gene expression of Treponema pallidum.. - Subsequently, the obtained mini- mum shared contents were subtracted from all the ge- nomes resulting in the variable contents, which were eventually compared with all the other strains for the calculation of the percentages of similarity. - The extrapolations of the pan-genomes from the Table 2 The list of genes related to PAI 2 of subsp. - it describes the number of distinct words in a document (or set of documents) as a function of the document length. - absence in other organisms of the same genus or closely related species [33]. - The sizes of the islands were compared with all the other strains via ACT (Artemis Comparison Tool) software [55]. - Fol- lowing the curation of the PAIs, the genes of all the islands in each strain were assessed for their presence/. - General information about 53 Treponema pallidum Strains used in this work. - List of all Treponema pallidum strains (with features) retrieved from the NCBI (National Center for. - The COG functional categories with detailed description of Core genes: The table showing the number of core genes of the complete dataset were classified by COG (Cluster of Orthologous Genes) functional category. - The COG functional categories with detailed description of Core genes: The table showing the number of core genes of the Pan Subsp_pallidum dataset were classified by COG (Cluster of Orthologous Genes) functional category. - The COG functional categories with detailed description of Core genes: The table showing the number of core genes of the Pan Subsp_pertenue dataset were classified by COG (Cluster of Orthologous Genes) functional category. - The heatmap analysis of 53 Strains of Treponema pallidum. - The names of the strains on the left side of the figure (vertically) are organized in the same order in the top part of the figure (horizontally). - TEN: Treponema pallidum subsp.. - TPA: Treponema pallidum subsp. - TPE: Treponema pallidum subsp. - Molecular differentiation of Treponema pallidum subspecies. - Global challenge of antibiotic-resistant Treponema pallidum.. - Genetics of Treponema: relationship between Treponema pallidum and five cultivable treponemes. - Identification, sequences, and expression of Treponema pallidum chemotaxis genes. - Tools for opening new chapters in the book of Treponema pallidum evolutionary history. - A defined syphilis vaccine candidate inhibits dissemination of Treponema pallidum subspecies pallidum. - Subfamily I Treponema pallidum repeat protein family: sequence variation and immunity. - Genome-scale analysis of the non- cultivable Treponema pallidum reveals extensive within-patient genetic variation. - A subpopulation of Treponema pallidum is resistant to phagocytosis: possible mechanism of persistence. - The tprK gene is heterogeneous among Treponema pallidum strains and has multiple alleles. - Sequence diversity of Treponema pallidum subsp. - The pan-genome of the animal pathogen Corynebacterium pseudotuberculosis reveals differences in genome plasticity between the biovar ovis and equi strains. - Comparison of the genome of the oral pathogen Treponema denticola with other spirochete genomes
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