Building through Thicket and Mesh: Modelling Structure and Assembly at the Gram-negative Outer Membrane
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Ryoo, David
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Abstract
The antimicrobial resistance (AMR) of microorganisms is quickly becoming a growing concern for the human population. In particular, such resistance in Gram-negative bacteria has become a difficult case to crack, as the outer membrane (OM) of the Gram-negative bacteria provides a substantial physical and chemical barrier against small molecules. In order to elucidate how the OM environment contributes to the AMR of Gram-negative bacteria, we studied three aspects that this environment provides, the virulence factor export by autotransporters (ATs), the biogenesis of the outer membrane proteins (OMPs), and the cell envelope that OM is a part of. We first focused on the virulence factor export or passenger domain secretion of ATs, and how the ATs will secrete through the BamA barrel of the larger β-barrel assembly machinery (BAM) complex. Then, we examined the plausibility of the hybrid model of folding and insertion by BAM complex from the simulations of both constructed hybrid models and cryoEM-resolved structures. Finally, we interrogated the OM and cell wall structure connected by Braun’s lipoprotein (Lpp) which more accurately depicts how the OM portion of the cell envelope would react against the turgor pressure. By examining these aspects of the Gram-negative bacteria, further developments to combat AMR of the Gram-negative bacteria can be made.
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2023-12-05
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Dissertation