The contribution of YfdX and Ail/OmpX-like proteins to Salmonella Typhimurium stress resistance and virulence

Palmero, Blanca (2021) The contribution of YfdX and Ail/OmpX-like proteins to Salmonella Typhimurium stress resistance and virulence. Masters thesis, University of East Anglia.

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Abstract

Salmonella is a Gram-negative, food-borne pathogen and a major cause of worldwide morbidity and mortality. Salmonella encounters a wide variety of stressors in its environments, including changes in pH and heat, antimicrobial compounds, and reactive oxygen and nitrogen species. These conditions can result in serious damage to the bacterium, in particular the cell wall. To combat this, envelope stress response (ESR) pathways are in place to sense and respond to protein damage induced by such conditions and restore envelope homeostasis. There is a degree of overlap in terms of environmental cues and regulon members across the ESR pathway, many of which are important for Salmonella infection.

We have been investigating genes that are co-regulated by more than one ESR, as we hypothesise that they will be more important for maintaining envelope homeostasis and might be potential therapeutic targets. We discovered that the hypothetical protein STM3030 and the outer membrane protein STM3031, which is an Ail/OmpX-like protein, were both transcriptionally regulated by the CpxR and BaeR ESR regulators in Salmonella. Both proteins have been associated with antibiotic resistance, with STM3030 having chaperone activity, and a Typhi homologue of STM3031 a role in adhesion to host cells.

This study aims to characterise the roles of STM3030 and STM3031 in the S. Typhimurium ESR and infection. Using single and double deletion mutants, we have identified a role for these proteins in adhesion of Salmonella Typhimurium to Caco-2 epithelial cells, as well as determined their role in a range of envelope damaging conditions.

The results of this study show that STM3030 and STM3031 cooperate during host cell adhesion, after which only STM3031 is needed for invasion of host cells, contradicting past studies, and revealing novel virulence functions of STM3030 and STM3031. This study highlights the need for further investigation into Salmonella molecular mechanisms of disease.

Item Type:	Thesis (Masters)
Faculty \ School:	Faculty of Science > School of Biological Sciences
Depositing User:	Chris White
Date Deposited:	22 Aug 2022 12:35
Last Modified:	22 Aug 2022 12:35
URI:	https://ueaeprints.uea.ac.uk/id/eprint/87541
DOI:

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