Characterisation of σE-regulated stress response proteins and their contributions to Salmonella physiology

Hews, Claire (2020) Characterisation of σE-regulated stress response proteins and their contributions to Salmonella physiology. Doctoral thesis, University of East Anglia.

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The ability of Salmonella to sense and respond to changing environmental conditions is central to its survival within a host and the food chain. The Gram-negative envelope forms a crucial barrier between the intracellular and harsh extracellular space and its maintenance is essential. The extracytoplasmic sigma factor, σE, is a major contributor to envelope homeostasis during exposure to stress-inducing conditions but much of its regulon remains poorly understood.

In this study, we aimed to understand the contribution of the σH- and σE-regulated small heat shock proteins (sHsps) IbpA, IbpB and AgsA and the σE-regulated putative stress response protein STM1250 to the Salmonella stress response. Due to shared regulation and sequence homologies, we hypothesised that functional overlap exists between these proteins and that they contribute to maintaining cell envelope homeostasis during stress.

We have identified novel roles for the sHsps and STM1250 in Salmonella survival against hydrogen peroxide-associated oxidative stress and the cationic antimicrobial peptide polymyxin B. Furthermore, we demonstrated that a quadruple deletion mutant is significantly attenuated in the intramacrophage environment. In contrast, single gene mutants were not significantly attenuated or sensitive, indicating that functional redundancy exists between these proteins. In addition, this study is the first to address the function of the hypothetical protein STM1250 which was shown to be required for a functional Salmonella acid tolerance

Considering their functional redundancy, we sought to investigate whether the proteins of interest may co-operate through protein-protein interactions. Initial bacterial two-hybrid results identified novel heterogenous interactions between the sHsps and STM1250.

Put together, we have demonstrated that Salmonella sHsps can protect against stresses beyond heat shock. Moreover, this study highlights that investigating functional redundancy between stress responsive proteins has the potential to identify those that are important to pathogenesis and may aid in identifying much needed new therapeutic targets.

Item Type: Thesis (Doctoral)
Faculty \ School: Faculty of Science > School of Biological Sciences
Depositing User: Chris White
Date Deposited: 16 Sep 2021 13:20
Last Modified: 16 Sep 2021 13:20


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