Use of zebrafish to study Shigella sonnei strain diversity and evolution

Prof Serge Mostowy (primary)
Department of Infection Biology
LSHTM
Prof Kathryn Holt (secondary)
Department of Infection Biology
LSHTM

Abstract

Shigella sonnei is an intracellular pathogen and the dominant cause of shigellosis globally. Zebrafish is a well-established model system to study host-pathogen interactions in vivo, and the Mostowy lab has recently shown it as valuable to study the pathogenesis and evolution of Shigella species. This project will use the Shigella-zebrafish infection model to investigate in vivo evolutionary phenomena indicated by recent genomics studies of S. sonnei from the Holt lab, including lineage-specific differences in host-pathogen interactions; functional effects of transposase activity (which interrupt some genes and up-regulate others); and in vivo fitness costs of AMR mechanisms in different strain backgrounds.


References

1. Gomes MC, Mostowy S. “The case for modelling human infection in zebrafish.” Trends in Microbiology 2019 in press

2. The HC, Thanh DP, Holt KE, Thomson NR, Baker S. “The genomic signatures of Shigella evolution, adaptation and geographical spread.” Nature Reviews Microbiology 2016 14(4):235-50. doi: 10.1038/nrmicro.2016.10 PMID: 26923111

3. Mazon-Moya M, Willis A, Torraca V, Boucontet L, Shenoy AR, Colucci-Guyon E, Mostowy S. “Septins restrict inflammation and protect zebrafish larvae from Shigella infection.” PLoS Pathogens 2017 13:e1006467. doi: 10.1371/journal.ppat.1006467 PMID: 28650995

4. Mostowy S, Boucontet L, Mazon Moya MJ, Sirianni A, Boudinot P, Hollinshead M, Cossart P, Herbomel P, Levraud JP, Colucci-Guyon E. “The zebrafish as a new model for the in vivo study of Shigella flexneri interaction with phagocytes and bacterial autophagy.” PLoS Pathogens 2013 9(9):e1003588. doi: 10.1371/journal.ppat.1003588 PMID: 24039575

5. Holt KE, Baker S, Weill FX, Holmes EC, Kitchen A, Yu J, Sangal V, Brown DJ, Coia JE, Kim DW, Choi SY, Kim SH, da Silveira WD, Pickard DJ, Farrar JJ, Parkhill J, Dougan G, Thomson NR. “Shigella sonnei genome sequencing and phylogenetic analysis indicate recent global dissemination from Europe.” Nature Genetics 2012 44(9):1056-9. doi: 10.1038/ng.2369 PMID: 22863732


BBSRC Area
Genes, development and STEM* approaches to biology
Area of Biology
EvolutionMicrobiology
Techniques & Approaches
BioinformaticsGeneticsImage ProcessingMicroscopy / ElectrophysiologyMolecular BiologySimulation / Modelling