The Contribution of Nitric Oxide Detoxification and Nitrous Oxide Production to Salmonella Pathogenesis

Johnston, Isabel (2017) The Contribution of Nitric Oxide Detoxification and Nitrous Oxide Production to Salmonella Pathogenesis. Doctoral thesis, University of East Anglia.

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Salmonella is responsible for millions of infections worldwide, with varied disease outcomes, ranging from localised gastroenteritis to a fatal systemic infection. As a facultative anaerobe, Salmonella is able to respire using nitrate as an alternative electron acceptor. This study highlights the role of two gaseous intermediates produced during nitrate respiration, nitric oxide (NO) and nitrous oxide (N2O), during Salmonella pathogenesis.
Building from previous studies, a link is drawn between the high level of production of N2O by Salmonella, and the metabolically expensive, and seemingly unimportant synthesis of vitamin B12. We demonstrate the importance of the vitamin B12 independent methionine synthase, MetE, both during nitrate respiration and for survival within macrophages. We hypothesise that when respiring on nitrate in the intestine Salmonella releases N2O which is detrimental to vitamin B12 availability and commensal survival in the intestine. Salmonella however is protected two-fold from the toxicity of N2O, by the presence of MetE, and by the ability to synthesise vitamin B12 de novo. This phenomenon is further investigated across multiple Salmonella serovars, with the indication that enteric strains produce both higher levels of vitamin B12 and N2O.
As well as during nitrate respiration, Salmonella also encounters NO exogenously when challenged by the host defense inside macrophages. Since NO is a highly toxic compound effective detoxification systems are essential for survival. A relationship between NO and tellurite resistance in Salmonella is shown. Three putative tellurite resistance proteins, TehB, STM1808 and YeaR were confirmed to provide resistance against tellurite in Salmonella and share functional redundancy in the anaerobic detoxification of NO and infection of macrophages. Using a suite of NO sensitive mutants, we also demonstrate a clear correlation between tellurite and NO sensitivity.
Collectively this study highlights two important aspects of the nitrogen cycle which contribute to pathogenesis in Salmonella.

Item Type: Thesis (Doctoral)
Faculty \ School: Faculty of Science > School of Biological Sciences
Depositing User: Megan Ruddock
Date Deposited: 16 May 2018 16:14
Last Modified: 16 May 2018 16:14


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