2. Abstract
The 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 ubiquitin-protein ligases may explain the differences in the infectious dose and disease severity between Shigella and EIEC pathotypes.
Impact statement Pathogenic 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 The datasets supporting the conclusions of this article and used scripts are available at https://github.com/zseferbekova/ShigellaProject. The authors confirm all supporting data have been provided in the article or as supplementary data files.
Competing Interest Statement
The authors have declared no competing interest.
