Novel proteins that affect Salmonella virulence
Advisor: Yu-Chu Chang
Location: Max-Planck Institute for Biology Tübingen
The outer membrane (OM) of Gram-negative bacteria serves as the first defense front against the surrounding stresses and plays a vital role in interacting with different host cells. The outer leaflet of this asymmetrical OM is composed of lipopolysaccharide (LPS), which contains a variety of exopolysaccharide structures. Although the biogenesis of LPS has been extensively studied, the works were primarily on the biosynthesis of the "Lipid A" base and the "inner core oligosaccharide." Another significant component of LPS is the highly variable polysaccharide outer core known as the O-antigen. The O-antigen repeating unit synthesizes primarily through the bacterial Wzx/Wzy dependent pathways. The integral membrane protein, Wzx, is a flippase responsible for flipping a lipid-linked oligosaccharide (LLO) out to the periplasmic side for further elongation. Although the general function of Wzx is known, the molecular mechanism of the flipping process needs further exploration. Knockout of Wzx in Salmonella also strongly decreases its virulence to the host cells.
The substrates of the Wzx protein family are undecaprenyl-pyrophosphate (UndPP) linked oligosaccharides on the lipid bilayer of the bacterial inner membrane. WzxPa from Pseudomonas has been shown to act as an antiporter using the H+ gradient as the driving force for substrate flipping. Since the Wzx has high sequence variation among different Gram-negative bacteria, the project will investigate if Salmonella Wzx also uses H+ as a coupling ion or other types of cations. Additionally, in vitro biochemical assays will be developed to directly detect the flipping process of the LLO substrates. Different oligosaccharide repeating units linked to the lipid carriers with fluorescent probes will be synthesized chemically for detecting purposes. With the development of a functional assay for Wzx, the functional mechanism of the protein can be more thoroughly characterized.
More information about the research of Yu-Chu Chang and a selection of recent publications can be found on his faculty page.
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Application deadline: 27 January 2025