High Rates of Genome Rearrangements and Pathogenicity of Shigella spp.

Abstract

Shigella are pathogens originating within the Escherichia lineage but frequently classified as a separate genus. Shigella genomes contain numerous insertion sequences (ISs) that lead to pseudogenisation of affected genes and an increase of non-homologous recombination. Here, we study 414 genomes of E. coli and Shigella strains to assess the contribution of genomic rearrangements to Shigella evolution. We found that Shigella experienced exceptionally high rates of intragenomic rearrangements and had a decreased rate of homologous recombination compared to pathogenic and non-pathogenic E. coli. The high rearrangement rate resulted in independent disruption of syntenic regions and parallel rearrangements in different Shigella lineages. Specifically, we identified two types of chromosomally encoded E3 ubiquitin-protein ligases acquired independently by all Shigella strains that also showed a high level of sequence conservation in the promoter and further in the 5′-intergenic region. In the only available enteroinvasive E. coli (EIEC) strain, which is a pathogenic E. coli with a phenotype intermediate between Shigella and non-pathogenic E. coli, we found a rate of genome rearrangements comparable to those in other E. coli and no functional copies of the two Shigella-specific E3 ubiquitin ligases. These data indicate that the accumulation of ISs influenced many aspects of genome evolution and played an important role in the evolution of intracellular pathogens. Our research demonstrates the power of comparative genomics-based on synteny block composition and an important role of non-coding regions in the evolution of genomic islands.

Chromosome-encoded IpaH ubiquitin ligases indicate non-human enteroinvasive 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 non-invasive E. coli and excluded them from the analysis. Additionally, we checked that non-invasive 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.…”

Pathogenicity and Its Implications in Taxonomy: The Brucella and Ochrobactrum Case

“…One of the best-known is the Shigella and Escherichia dichotomy. Even though Shigella and Escherichia strains are phylogenetically entwined, they are maintained apart because of significant pangenomic differences, including chromosomal sizes, insertion sequence-mediated pseudogenization, acquisition of the pINV virulence plasmid, and above all, different typologies [ 32 , 65 ]. The problem is evident when the Mycobacterium cluster (the equivalence example given in [ 9 ]) is examined in detail and compared with the Ochrobactrum - Brucella case.…”

PaReBrick: PArallel REarrangements and BReaks identification toolkit

“…Such beneficial rearrangements may occur independently in different strains, which leads to instances of parallel adaptation to new environments or phenotypic diversity ( Seferbekova et al , 2021 ). Phenotypic diversity in clonal populations is shaped by a mechanism of reversible alternation between genetic states known as phase variation ( Trzilova and Tamayo, 2021 ).…”

“…Presently, the identification of parallel rearrangements providing adaptation or phenotype switching is performed by laborious manual inspection of complex phylogenetic and genomic data ( Bochkareva et al , 2018 ; Seferbekova et al , 2021 ; Shelyakin et al , 2019 ). The pipelines used in such studies involve the construction of phylogenetic trees, identification of synteny blocks, and in-house scripting to identify parallel synteny block inversions and deletions on the phylogeny.…”