High rates of genome rearrangements and pathogenicity ofShigellaspp

Abstract

KeywordShigella, Escherichia coli, genomic rearrangements, pathogens, recombination, IS, ipaH AbstractThe genus Shigella comprises a polyphyletic group of facultative intracellular pathogens that evolved from Escherichia coli. Shigella genomes have accumulated mobile elements, which may have been caused by decreased effective population size and concomitant reduction of purifying selection that allowed their proliferation. Here, we investigated the interplay of the accumulation of genomic repeats with genomic rearrangements and their impact on adaptation in bacterial evolution. We studied 414 genomes of E. coli and Shigella strains to assess the contribution of genomic rearrangements to Shigella pathoadaptation. We show that Shigella accumulated a variety of insertion sequences (ISs), experienced exceptionally high rates of intragenomic rearrangements and had a decreased rate of homologous recombination. IS families differ in the expansion rates in Shigella lineages, as expected given their independent origin. In contrast, the number of IS elements and, consequently, the rate of genome rearrangements in the enteroinvasive E. coli strain (EIEC) strain are comparable to those in other E. coli. We found two chromosomal E3 ubiquitin-protein ligases (putative IpaH family proteins) that are functional in all Shigella strains, while only one pseudogenised copy is found in the EIEC strain and none in other E. coli. Taken together, our data indicate that ISs played an important role in the adaptation of Shigella strains to a intracellular lifestyle and that the composition of functional types of ubiquitinprotein ligases may explain the differences in the infectious dose and disease severity between Shigella and EIEC pathotypes. Impact statementPathogenic Escherichia coli frequently cause infections in humans. Many E. coli exist in nature and their ability to cause disease is fueled by their ability to incorporate novel genetic information by extensive horizontal gene transfer of plasmids and pathogenicity islands. The emergence of antibiotic-resistant Shigella, which is a pathogenic form of E. coli, coupled with the absence of an effective vaccine against them, highlights the importance of continued study of these pathogenic bacteria. Our study contributes to the understanding of genomic properties associated with molecular mechanisms underpinning the pathogenic nature of Shigella. We show the contribution of insertion sequences in adaptation of these intracellular pathogens and indicate a role of chromosomal ipaH genes in Shigella pathogenesis. The approaches developed in our study are broadly applicable to investigation of genotype-phenotype correlation in historically young bacterial pathogens. Data summary

Chromosome-encoded IpaH ubiquitin ligases indicate non-human pathogenic Escherichia

“…The presence of IpaH effectors is one of the markers used for Shigella serotyping (36), however, less than a half of sequenced genomes had the entire set of the ipaH genes. Contrary to previous observations on smaller datasets (32), none of the ipaH genes are common to all Shigella strains, and the phyletic patterns of the ipaH genes suggest numerous independent gene losses. While the targets of some IpaH proteins are unknown, some proteins have shown to affect the same pathway at different stages, working together to cause disease (3).…”

“…These samples were extracted from soil, stream sediment, and Antarctic lichen so we classified them as noninvasive E. coli and excluded them from the analysis. Additionally, we checked that noninvasive E. coli strains did not have any of these virulence determinants using the set of 414 E. coli + Shigella genomes from (32). In 17 assemblies, the plasmids were absent but we found chromosomal ipaH genes.…”

PaReBrick: PArallel REarrangements and BReakpoints identification toolkit

“…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.…”

“…Nevertheless, beneficial rearrangements are also known, such as the ones providing acquisition of new functions, phenotype switching, or fast genome reduction [2]. Such rearrangements may occur independently in different strains providing parallel adaptation to new environments [17] or phenotypic diversity into clonal populations [20]. The latter is shaped by phase variationthe mechanism of reversible alternation between genetic states.…”