Genomic analysis of the emergence of 20th century epidemic dysentery

Background Shigella dysenteriae type 1 ( Sd 1) causes recurrent epidemics of dysentery associated with high mortality in many regions of the world. Sd 1 infects humans at very low infectious doses (10 CFU), and treatment is complicated by the rapid emergence of antibiotic resistant Sd 1 strains. Sd 1 is only detected in the context of human infections, and the circumstances under which epidemics emerge and regress remain unknown. Results Phylogenomic analyses of 56 isolates collected worldwide over the past 60 years indicate that the Sd 1 clone responsible for the recent pandemics emerged at the turn of the 20 th century, and that the two world wars likely played a pivotal role for its dissemination. Several lineages remain ubiquitous and their phylogeny indicates several recent intercontinental transfers. Our comparative genomics analysis reveals that isolates responsible for separate outbreaks, though closely related to one another, have independently accumulated antibiotic resistance genes, suggesting that there is little or no selection to retain these genes in-between outbreaks. The genomes appear to be subjected to genetic drift that affects a number of functions currently used by diagnostic tools to identify Sd 1, which could lead to the potential failure of such tools. Conclusions Taken together, the Sd 1 population structure and pattern of evolution suggest a recent emergence and a possible human carrier state that could play an important role in the epidemic pattern of infections of this human-specific pathogen. This analysis highlights the important role of whole-genome sequencing in studying pathogens for which epidemiological or laboratory investigations are particularly challenging.