Investigating Bacterial Filamentation as a Survival Strategy for Infection
- Publication Type:
- Thesis
- Issue Date:
- 2022
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| 01front.pdf | contents and abstract | 541.37 kB | |||
| 02whole.pdf | thesis | 13.35 MB |
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Numerous bacteria, both pathogenic and non-pathogenic, can change shape in response to environmental cues for survival; a phenomenon called morphological plasticity. Our understanding of this plasticity is based mainly on stress-free growth conditions in the laboratory, making it difficult to determine its role in bacterial responses to the pressures of ‘real-world’ environments. One such shape that has drawn research interest is that of filaments, formed predominately from rod-shaped bacteria such as Escherichia coli. Filamentous uropathogenic E. coli appear to play important roles in combating host defences during urinary tract infections through their decreased engulfment by phagocytic immune cells like macrophages. Bacterial filamentation, as a strategy to avoid engulfment during infections, is a possible virulence pathway that has been highlighted in previous research but is yet to be fully explored. Investigations in this area could reveal novel insights into bacterial-host interactions leading to the discovery of new targets for future treatments.
The aim of this thesis was to investigate how E. coli rods and filaments differ in their interactions with human macrophages. Conditions were established for creating viable populations of filamentous E. coli (strain UTI89) using antibiotics and genetic methods. Quantification of intracellular bacteria revealed that the longer the filament, the less likely it is to be engulfed. Changing the shape of UTI89 showed that spherical cells are more readily engulfed than rod-shaped cells of similar volume. However, engulfment of spheres decreases as volume increases, indicating that the shape of bacteria can influence engulfment to a certain extent before size and length become limiting.
The importance of bacterial surface was investigated by blocking macrophage mannose binding of UTI89 rods and filaments and using fimH-deleted UTI89. Surprisingly, while blocking mannose binding resulted in reduced intracellular numbers of rods and filaments, deletion of fimH resulted in increased numbers and abolished macrophage length preference for rods. THP-1 macrophages and human monocyte derived macrophages (HMDMs) were used in this research. HMDMs behaved similarly to THP-1 macrophages, with the exception that HMDMs had detectable cytokine levels and their viability after infection with UTI89 rods and filaments differed. Significantly lower cytokine responses and viability were observed for HMDMs infected with filaments compared to those with rods.
This research has identified differences between UTI89 rods and filaments in the context of human macrophage interactions, providing a foundational understanding of filament engulfment. Eventually, this knowledge may reveal potential targets for the novel treatment of infections.
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