Investigating the mechanisms of pathogenesis of Shigella sonnei
File(s)
Author(s)
Watson, Jayne
Type
Thesis or dissertation
Abstract
Globally, S. flexneri is responsible for most Shigellosis cases and is associated with disease in developing countries. In developed countries, or those with recently improved socioeconomic conditions, S. sonnei is responsible for most Shigellosis cases. As more countries undergo improvements, S. sonnei is emerging as an important pathogen. However, awareness of Shigella pathogenesis has come from studies using S. flexneri. Recent studies have identified important aspects of S. sonnei pathogenesis – a group 4 capsule protecting S. sonnei from serum-mediated killing, a T6SS increasing gut colonisation, and an important cell adhesin.
It is unclear why S. sonnei is dominant in higher socioeconomic areas. One theory was that S. sonnei used amoebae as an environmental host, protecting it from water sanitation. However, in this study, while both S. sonnei and S. flexneri survive in long-term co-culture with amoebae, neither survive intracellularly short- or long-term. Interestingly, S. sonnei was able to survive better than S. flexneri in low-nutrient media used for long-term studies, and in environmental water sources, perhaps explaining the dominance of S. sonnei in developed countries.
During mammalian infection S. flexneri induces macrophages pyroptosis, allowing subsequent basolateral invasion of epithelial cells. In this study, S. sonnei induced minimal macrophage pyroptosis, explained by less cytosolic S. sonnei as a result of reduced phagocytosis and vacuole escape. Epithelial cell interactions of S. sonnei and S. flexneri were also compared. As previously reported, the S. sonnei group 4 capsule impeded epithelial cell invasion. Following invasion, S. sonnei replicated faster than S. flexneri, and the group 4 capsule was responsible for this.
This study identifies differences between S. sonnei and S. flexneri and highlights the need for further research.
It is unclear why S. sonnei is dominant in higher socioeconomic areas. One theory was that S. sonnei used amoebae as an environmental host, protecting it from water sanitation. However, in this study, while both S. sonnei and S. flexneri survive in long-term co-culture with amoebae, neither survive intracellularly short- or long-term. Interestingly, S. sonnei was able to survive better than S. flexneri in low-nutrient media used for long-term studies, and in environmental water sources, perhaps explaining the dominance of S. sonnei in developed countries.
During mammalian infection S. flexneri induces macrophages pyroptosis, allowing subsequent basolateral invasion of epithelial cells. In this study, S. sonnei induced minimal macrophage pyroptosis, explained by less cytosolic S. sonnei as a result of reduced phagocytosis and vacuole escape. Epithelial cell interactions of S. sonnei and S. flexneri were also compared. As previously reported, the S. sonnei group 4 capsule impeded epithelial cell invasion. Following invasion, S. sonnei replicated faster than S. flexneri, and the group 4 capsule was responsible for this.
This study identifies differences between S. sonnei and S. flexneri and highlights the need for further research.
Version
Open Access
Date Issued
2019-03
Date Awarded
2019-09
Copyright Statement
Creative Commons Attribution NonCommercial Licence
Advisor
Clements, Abigail
Sponsor
Medical Research Council (Great Britain)
Publisher Department
Life Sciences
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)