Professor Kate Baker BVSc PhD MRCVS FHEA

Infectious disease studies in lower and middle income nations (LMIC) are often complicated by a lack of systematic surveillance. We have previously engaged with existing surveillance networks (such as the foodborne illness transmission network PulseNet Latin America) to create a genomic benchmark for new pathogen databases (https://microreact.org/project/Shigella_sonnei_in_Latin_America). To continue our work to address the Shigella disease burden in LMIC, we are studying the systematically-collected Shigella isolates from GEMS, a five-year aetiological study on moderate to severe diarrhoeal disease in children <5 years conducted across seven nations in South Asia and SubSaharan Africa. By studying the genome sequences, we can identify Shigella sublineages most responsible for disease in this key demographic, evaluate local and regional antimicrobial treatment guidelines against pathogen AMR signatures (genotypic and phenotypic AMR correlate well in Shigella), and work to aid the use of vaccines for Shigella in these regions. This work is also complemented by a nation-wide study of shigellosis in South Africa.

The occurrence of highly AMR Shigella among MSM is an important public health issue and represents a tractable model for studying the broader crisis of highly AMR-STIs in MSM, including gonorrhoea. A large international collaboration, we identified a Shigella sublineage that is emerging globally (UK, France, Canada, Australia) among MSM and is associated with transmissible AMR (plasmid-borne macrolide resistance). This work was then built on to identify that the resistance plasmid was moving among different sublineages of Shigella transmitting among MSM. Plasmid acquisition drove epidemics of new Shigella sublineages (https://www.youtube.com/watch?v=KiBgsnYoJac).

We are currently extending this work by correlating the behaviour of the genetic determinants of AMR in the laboratory to the public-health level incidence data to develop models for evaluating antimicrobial stewardship strategies and determine whether the microbiota play a role in AMR transmission among MSM-associated Shigella strains. For this work, we integrate laboratory experimentation, clinical sampling, genomics epidemiology and mathematical modelling.

Underpinning our understanding of the genomic epidemiology of pathogens is a fundamental understanding of their evolution. Historical isolates of Shigella show targeted gain of AMR and virulence characteristics over time (e.g. this WW1 isolate study: https://www.youtube.com/watch?v=u-fbd9JpiMs). We are now seeking other genes with similar temporal signatures to AMR in a functionally-agnostic way to determine what contributes to pathogen persistence in populations over time.