Loss of Functional PMRA as Pathoadaptaion in the Shigella Spp

Shigella spp. are pathogens responsible for the global burden of diarrhoeal disease. The genus is comprised of four species: Shigella sonnei, Shigella boydii, Shigella flexneri and Shigella dysenteriae, each phylogenetically different but phenotypically and pathogenically similar. Previous work by the McPhee lab examining the two-component signalling cascade PhoPQ-PmrD-PmrAB identified a mutation in pmrD which resulted in the loss of PmrD protein in S. flexneri M90T. Here, I investigate whether there is a loss of PmrD-PmrAB signalling cascade in other strains of Shigella besides S. flexneri M90T. Using pangenome analysis we construct a core-gene phylogeny and find our results in agreement with previous findings that Shigella spp has multiple origins of evolution. In our work we also show their genomes spread over five prominent clusters, interspersed within Escherichia genomes. Further, we look for genomic variations of pmrD and pmrA, and identified a total of 11 distinct variations; 4 of pmrD and 7 of pmrA. Using in vitro microbiology techniques, we found that one variation, a truncated pmrA present in a subset of S. dysenteriae strains did not maintain PmrAB-regulated polymyxin B resistance. We also show that the PmrD-PmrAPmrB signalling cascade does not modulate O antigen length in a dominate variant of pmrD present in all S. flexneri strains or the truncated pmrA present in some S. dysenteriae strains.