The genomics, evolution, and spread of Shigella species in Asia

The bacterial genus Shigella remains a significant cause of diarrhoea in young children, particularly in tropical and developing countries. Effective clinical management and public health policy implementation require an in-depth understanding of the pathogen’s evolution and epidemiology. This thesis set out to utilize genomic and phylogenetic analyses to investigate Shigella’s life history in several settings. Firstly, I focused on S. sonnei exhibiting escalating resistance to fluoroquinolones, which are the recommended treatment for shigellosis. I showed that extant geographically dispersed fluoroquinolone resistant S. sonnei emerged as a single clone in South Asia around 2007. This clone then spread internationally, creating sustained transmissions in Southeast Asia and Europe. Secondly, examination of a vast historical Shigella sequencing dataset from Southeast Asia showed that contemporary regional Shigella populations are progenies of relatively recent introductions, mostly during the 1980s-1990s. Intraspecific clonal replacement, occurring in both S. sonnei and major S. flexneri serotypes, was frequent and linked with resistance to contemporaneously used antimicrobials. The secondary aim of this thesis was to explore the alternations of the gut microbiota in response to infectious diarrhoea in children. I found that the diarrhoeal faecal microbiome could either generally resemble or greatly diverge from that of a healthy state. Escherichia and oral bacterial commensals were found to be consistently enriched in the diarrhoeal faecal microbiome. These studies demonstrate the versatility of applying sequencing to studying diarrhoea in endemic regions, enhancing our current understanding of this public health problem.