Virulence plasmid pINV as a genetic signature for Shigella flexneri phylogeny

Abstract

Shigella flexneri is a major health burden in low- and middle-income countries, where it is a leading cause of mortality associated with diarrhoea in children, and shows an increasing incidence among travellers and men having sex with men. Like all Shigella spp., S. flexneri has evolved from commensal Escherichia coli following the acquisition of a large plasmid pINV, which contains genes essential for virulence. Current sequence typing schemes of Shigella are based on combinations of chromosomal genetic loci, since pINV-encoded virulence genes are often lost during growth in the laboratory, making these elements inappropriate for sequence typing. By performing comparative analysis of pINVs from S. flexneri strains isolated from different geographical regions and belonging to different serotypes, we found that in contrast to plasmid-encoded virulence genes, plasmid maintenance genes are highly stable pINV-encoded elements. For the first time, to our knowledge, we have developed a S. flexneri plasmid multilocus sequence typing (pMLST) method based on different combinations of alleles of the vapBC and yacAB toxin–antitoxin (TA) systems, and the parAB partitioning system. This enables typing of S. flexneri pINV plasmids into distinct ‘virulence sequence types’ (vSTs). Furthermore, the phylogenies of vST alleles and bacterial host core genomes suggests an intimate co-evolution of pINV with the chromosome of its bacterial host, consistent with previous findings. This work demonstrates the potential of plasmid maintenance loci as genetic characteristics to study as well as to trace the molecular phylogenesis of S. flexneri pINV and the phylogenetic relationship of this plasmid with its bacterial host.

Genomic, transcriptomic, and phenotypic differences among archetype Shigella flexneri strains of serotypes 2a, 3a, and 6

“…Approximately 80% of the virulence plasmid content is conserved between the three archetype strains ( Fig. 3 ), consistent with recent analysis ( 57 ). This level of conservation is irrespective of the archetype reference plasmid used, indicating that there is a conserved plasmid core (Table S2).…”

Genomic plasticity is a blueprint of diversity inSalmonellalineages

“…All these phages belong to the kingdom Heunggongvirae, phylum Uroviricota, and class Caudoviricetes. Within Caudoviricetes, 25% (43,316) of the phage regions belong to the genus Peduovirus, 18% (30,402) to the genus Lederbergvirus and 10% (16,568) to the genus Felsduovirus (Fig. 1e).…”

“…1). Among the different plasmid schemes, Shigella flexneri (virulence plasmid pINV 43 ) and IncHI2 plasmids are those most frequently associated with stress resistance genes, but IncA/C plasmids, due to their abundance, are responsible for the movement of most stress resistance genes ( Fig. 2d , Supplementary Table 8 ).…”

A Tale about Shigella: Evolution, Plasmid, and Virulence

“…Taken together, the diverse combination of maintenance systems of the sonnei and the flexneri subgroups determines the stability of their respective versions of pINV, which affects their pathogenesis and epidemiology. Accordingly, these maintenance systems are practical for typing Shigella strains because they are better conserved than T3SS-related genes and reproduces the phylogeny obtained using chromosomal genes [ 64 ]. This supports the importance of these maintenance systems in the pathogenesis and the evolution of Shigella .…”