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In recent years there has been a shift in the primary etiological agent of shigellosis, a human-specific disease also known as bacillary dysentery, in many developing nations. Shigella sonnei, historically associated with more developed countries, has been observed to be rapidly replacing Shigella flexneri as the most prevalent species in many of these regions. Identifying the underlying reasons for this species shift is important for developing effective management strategies to control the disease, and more generally develop our knowledge of the spread of pathogens.
Our research is tackling this question through three main strategies.
1) Whole Genome Sequence (WGS) analysis:
Next-Generation Sequence (NGS) data has greatly improved our understanding of bacterial genomic evolution, particularly with identifying antibiotic resistance mutations. We are using WGS data to investigate the how the evolution of antibiotic resistance may have contributed to the spread of S. sonnei in developing nations. Our research focuses on identifying novel mutations and notably how compensatory mechanisms may have evolved to increase bacterial fitness.
2) Microbiology and laboratory experiments:
Recent evidence has shown there are demographic and geographical differences between the distribution of shigellosis infections caused by S. sonnei and S. flexneri, with the increase in S. sonnei associated with improvements in water quality and sanitation. To test this theory further we are working with live strains of Shigella spp., conducting experiments on the survival of S. sonnei and S. flexneri in varying concentrations of disinfectants that may indicate differences in tolerance to environments associated with improving sanitation. We are also utilizing RNA-seq to identify the expression changes on a genomic level and gain an insight into the cellular mechanisms that may be involved in chemical tolerance.
3) Simulation based modeling:
The spread of infectious diseases can also be influenced by the mode of transmission. Whilst all Shigella spp. are predominately categorized as transmitted through the fecal-oral route, there is evidence that the bacteria can survive for extended periods in the environment in waterways or deposited on fomites. We are developing models of disease transmission that include the potential for environmental reservoirs that may alter the evolution and spread of endemic diseases.
