A correlation between tellurite resistance and nitric oxide detoxification in Salmonella Typhimurium

Callow, Chloe (2022) A correlation between tellurite resistance and nitric oxide detoxification in Salmonella Typhimurium. Masters thesis, University of East Anglia.

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Salmonella are important enteric pathogens that are responsible for causing various diseases from gastroenteritis to systemic typhoid fever. Salmonella are a major contributor to morbidity and mortality worldwide. Crucial to their pathogenesis is the survival in harmful conditions elicited by the host immune system, one of these being reactive oxygen and nitrogen species (ROS/RNS). These are produced by macrophages and neutrophils in an attempt to eliminate pathogens. Salmonella, have the unique ability to colonise macrophages and have dedicated nitric oxide (NO) detoxification systems. There are three prominent metalloenzymes (HmpA, NorVW and NrfA) heavily researched in the literature for NO detoxification. Previous work suggested that more proteins are responsible for the nitrosative stress response with these being regulated by the nitric oxide sensitive transcriptional repressor, NsrR.
This study demonstrates a relationship between three putative tellurite resistance proteins regulated by NsrR (STM1808, YeaR and TehB) and NO detoxification. A Functional redundancy between these proteins was observed for anaerobic protection against NO and tellurite. Furthermore, this study identified that proteins responsible in NO protection such as HmpA and YtfE also provide resistance to tellurite during aerobic and anaerobic conditions, respectively. Tellurite resistant Salmonella strains were evolved by continued passage in this study that consequently had altered H2O2 resistance profiles and increased sensitivity to antibiotics. However, these strains were not significantly attenuated during macrophage survival or during the presence of NO in vitro. Additionally, the hypothetical protein YgbA, which has predicted roles in NO detoxification, was found to be important to Salmonella survival in macrophages. However, in vitro NO exposure with the NO donor deta NONOate only showed a role for anaerobic protection.

Item Type: Thesis (Masters)
Faculty \ School: Faculty of Science > School of Biological Sciences
Depositing User: Nicola Veasy
Date Deposited: 07 Apr 2022 13:42
Last Modified: 07 Apr 2022 13:42
URI: https://ueaeprints.uea.ac.uk/id/eprint/84515


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