The interaction of Salmonella Typhimurium with host derived lipids

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Rooke, Jessica Louise ORCID: https://orcid.org/0000-0003-1258-4018 (2019). The interaction of Salmonella Typhimurium with host derived lipids. University of Birmingham. Ph.D.

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Abstract

Autotransporters are some of the most abundantly secreted proteins in Gram-negative bacteria. Many of these proteins function as virulence factors. S.enterica serovar Typhimurium has five autotransporter proteins: SadA; ApeE; MisL; YaiU; and ShdA. Here, the outer membrane biogenesis and virulence properties of the S. Typhimurium autotransporters have been investigated. The outer membrane biogenesis of the multimeric autotransporter SadA was shown to be dependent upon BamA and BamD, which are essential components of the β-barrel assembly machinery complex, but the non-essential components, BamB, C and E, are not required. Contrary to a report in the literature, the translocation assembly module complex is also not required for SadA secretion. ApeE is a classical autotransporter that has a GDSL lipase motif. ApeE was shown to have phospholipase B activity, with the ability to cleave acyl chains of phospholipids. The phospholipase activity of ApeE was inhibited by the serine lipase inhibitor methyl arachidonyl fluorophosphonate. Using an in vivo murine infection model, bacterial survival at 21 days post infection in gallbladders of mice, and efficient faecal shedding, required a functional ApeE protein. ApeE was also required for S. Typhimurium to utilise lyso-phosphatidylcholine as a sole carbon source for growth. It is proposed that Salmonella survival in the mouse gallbladder depends on the ability of ApeE to hydrolyse bile phospholipids for use as a nutrient source in vivo.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

Supervisor(s):