Sobkowiak, Benjamin Robert; (2017) The genetics and epidemiology of Shigella sonnei and Shigella flexneri in Vietnam. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Shigella sonnei is rapidly emerging as the primary agent of bacillary dysentery, or shigellosis, in many developing countries, replacing the historically more prevalent species, S. flexneri, in these regions. There have been various theories proposed to explain this phenomenon, including environmental changes and increased antimicrobial use, though the precise reasons for this shift are still uncertain. Here I present four studies investigating key ecological and genetic differences between S. sonnei and S. flexneri from a region that has undergone this pattern of species replacement, Vietnam. This work combines experimental and bioinformatics techniques with the aim of identifying the extent that differences in disinfectant sensitivity, chromosomal antimicrobial resistance profiles and gene content will contribute to the successful spread of S. sonnei over S. flexneri. Firstly, I conducted in vitro experimental work to characterise differences between species with respect to resistance to chlorine disinfection and tolerance to the detergent SDS. The mechanisms by which the bacteria respond to this treatment, in particular the role of efflux pumps, were then explored to determine whether any informative variation in these systems will explain any differences in disinfectant sensitivity. The availability of high quality whole genome sequences for ~150 of each Shigella species allowed for robust bioinformatics work to describe genomic variation between species. These sequences are used to detect key resistance mutations in each species and look for associated fitness compensating mutations. Finally, the complete genome sequence of all coding regions in each strain was de novo assembled to look for species-level gene content variation that might contribute to functional differences between S. sonnei and S. flexneri. The results of these studies show that there are clear biological differences between S. sonnei and S. flexneri, though more work is necessary to fully elucidate the reasons for the species replacement in developing countries.

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