Micro-evolution of three Streptococcus species: selection, antigenic variation, and horizontal gene inflow

Abstract

Background: The genus Streptococcus comprises pathogens that strongly influence the health of humans and animals. Genome sequencing of multiple Streptococcus strains demonstrated high variability in gene content and order even in closely related strains of the same species and created a newly emerged object for genomic analysis, the pan-genome. Here we analysed the genome evolution of 25 strains of Streptococcus suis, 50 strains of Streptococcus pyogenes and 28 strains of Streptococcus pneumoniae. Results: Fractions of the pan-genome, unique, periphery, and universal genes differ in size, functional composition, the level of nucleotide substitutions, and predisposition to horizontal gene transfer and genomic rearrangements. The density of substitutions in intergenic regions appears to be correlated with selection acting on adjacent genes, implying that more conserved genes tend to have more conserved regulatory regions. The total pan-genome of the genus is open, but only due to strain-specific genes, whereas other pan-genome fractions reach saturation. We have identified the set of genes with phylogenies inconsistent with species and non-conserved location in the chromosome; these genes are rare in at least one species and have likely experienced recent horizontal transfer between species. The strain-specific fraction is enriched with mobile elements and hypothetical proteins, but also contains a number of candidate virulence-related genes, so it may have a strong impact on adaptability and pathogenicity. Mapping the rearrangements to the phylogenetic tree revealed large parallel inversions in all species. A parallel inversion of length 15 kB with breakpoints formed by genes encoding surface antigen proteins PhtD and PhtB in S. pneumoniae leads to replacement of gene fragments that likely indicates the action of an antigen variation mechanism. Conclusions: Members of genus Streptococcus have a highly dynamic, open pan-genome, that potentially confers them with the ability to adapt to changing environmental conditions, i.e. antibiotic resistance or transmission between different hosts. Hence, integrated analysis of all aspects of genome evolution is important for the identification of potential pathogens and design of drugs and vaccines.

PaReBrick: PArallel REarrangements and BReakpoints identification toolkit

“…The PaReBrick tool detected the inversion between PhtB and PhtD genes as an event with the highest parallelism score (Supplementary Fig.S3) This inversion was previously shown to be respon for antigenic variation affecting surface antigens, encoded by PhtB and PhtD genes [18, 19]. PaReBrick detected nine strains across the phylogenetic tree that have this fragment inverted, including five strains that were identified in [18]. Moreover, PaReBrick detected additional rearrangement events affecting these adjacencies in five strains.…”

“…A strategy that may allow fast and cheap prediction of putative mechanisms of variation is the computational analysis of genomes focusing on genomic repeats and screening for reversible genome rearrangements. For instance, in the human pathogen Streptococcus pneumoniae , reversible inversions affecting surface antigens, encoded by phtB and phtD genes, were revealed computationally and confirmed experimentally [18, 19].…”

“…However, identification of rearrangements responsible for parallel evolution or phenotype switching requires laborious manual inspection of the composition and order of synteny blocks across the species’ phylogenetic tree and verification of the consistency of evolutionary events with tree topology [1, 18, 17]. Here we introduce PaReBrick, a method to identify and visualise parallel rearrangements in bacterial populations.…”

Pathogenicity and drug resistance of animal streptococci responsible for human infections

“…The capsular polysaccharide with a continually changing structure also influences avoidance of the host’s immune system response [5]. The close phylogenetic relationship, capacious pangenome and easy changeability allow bacterial of the genus Streptococcus to adapt to new environmental conditions and new hosts [6].…”

Cytotoxic Potential of Purified Arginine Deiminase from Streptococcus spp

“…It is irreplaceable for synthesis of proteins, urea, polyamines, agmatine and amino acids like glutamate and proline. The enzymes implicated in the three steps of the pathway are arginine deiminase (ADI, EC 3.5.3.6), ornithine transcarbamylase (OTC, EC 2.1.3.3), and carbamate kinase (CK, EC 2.7.2.2) (3) . ADI pathway is a multi-enzyme pathway encoded by arc operons genes named arcA, arcB, and arc, which hydrolyze arginine to ornithine, with the byproducts of ammonia, CO 2 and ATP (4) .…”