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Title: Establishing the Streptococcus pyogenes model of infection in the zebrafish embryo
Author: Michailidis, Dimitrios
ISNI:       0000 0004 8510 5986
Awarding Body: University of Sheffield
Current Institution: University of Sheffield
Date of Award: 2019
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Streptococcus pyogenes is a bacterium that colonises the human oropharynx asymptomatically. It is also a common cause of mild skin and throat infections. These can develop into invasive tissue disease and post-immune sequelae. In order to understand how S. pyogenes causes disease, several animal models have been used. My study has developed and interrogated the zebrafish embryo systemic model of infection. The first part of this work, involved analysis of the virulence of the H293 (emm89), H305 (emm1), and HSC5 (emm14) S. pyogenes strains, via zebrafish embryo survival assays. This revealed that H293 was the least virulent, and thus more amenable to study within experimental parameters. A study of bacterial population dynamics during infection suggested the presence of a bottleneck, where the immune system regulates growth of S. pyogenes for up to 8 hours post-infection. After this point, with an infectious dose that leads to approximately 50% host survival, either rapid bacterial growth and host mortality or decline in bacterial numbers was seen. Intravital microscopy revealed that phagocytes ingest S. pyogenes very early after infection, with macrophages containing more bacteria than neutrophils. Interestingly, by 8 hours post-infection, macrophages were found completely saturated with bacteria or empty, with concomitant extracellular S. pyogenes. The role of phagocytes as the immunological bottleneck was verified as their ablation led to uncontrolled bacterial proliferation. The role of other bacteria, and their products, in the initiation of S. pyogenes infection was then determined. Based on my findings, I have established a temporal and spatial model of S. pyogenes infection in the zebrafish embryo. This sets the scene for the determination and analysis of host-pathogen interactions to aid the development of new control regimes.
Supervisor: Foster, Simon Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available