What factors contribute to the long-term persistence of Shigella species as pathogens?

Bacteria of the genus Shigella cause 51 million cases of foodborne diarrhoeal illness and 100,000 deaths per annum globally, and understanding the factors that drive their long-term success will aid their ongoing management and translate to other pathogenic enteric bacteria. Shigellae are recognised as priority organisms because of their increasing antimicrobial resistance, which is frequently carried on plasmids stabilised by toxin-antitoxin systems. Toxin-antitoxin systems also have a role in maintaining the large virulence plasmid of Shigella and are located on the bacterial chromosome. A comparative genomic study of four Shigella genomes spanning the clinical introduction of antimicrobials (1915 - 2014) suggested that gene acquisition in Shigella acted to increase antimicrobial resistance, virulence and immune evasion, and similar studies comparing modern and pre-antibiotic era Klebsiella pneumoniae isolates showed increasing disinfectant resistance. These studies demonstrate that factors crucial to the long-term success of pathogenic bacteria are enriched in modern bacterial collections relative to historical ones.

The pre-antibiotic era Murray collection of Enterobacteriaceae were recently whole genome sequenced to provide a public resource for the scientific community and include many shigellae isolated between 1917 and 1943. Several thousand more modern (i.e. 1950s - 2018) isolates of Shigella have been sequenced for other studies. Through bioinformatic analysis of these existing data sets, this project will characterise the dynamic changes in the genetic composition of shigellae over the last 100 years to identify factors that have contributed to the long-term success of these pathogens, with a focus on antimicrobial resistance determinants and their maintenance through toxin-antitoxin systems. Selected toxin-antitoxin systems will be identified bioinformatically and characterised in complementary laboratory studies. Achieving these objectives will provide unprecedented overview into how AMR, toxin-antitoxin systems and other factors contribute to the long-term success of enteric bacteria, and provide a unique insight on how toxin-antitoxin systems impact the accumulation of AMR.