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Probing the molecular level details of bacterial outer membrane vesicles and their parent bacteria: A simulation approach

Probing the molecular level details of bacterial outer membrane vesicles and their parent bacteria: A simulation approach
Probing the molecular level details of bacterial outer membrane vesicles and their parent bacteria: A simulation approach
Gram-negative bacteria have an unusual cell envelope that contains an inner cytoplasmic lipid membrane and an outer bacterial lipid membrane. The outer bacterial lipid membrane produces outer membrane vesicles that regulate bacterial pathogenesis processes. The outer membrane vesicles transport virulence factors from bacteria to host cell surfaces and the vesicles then move into the host cell cytosol. Computer simulations were conducted here in this thesis to understand how outer membrane vesicles pass through host cell surfaces independently of any membrane protein effects. The simulations suggest that outer membrane vesicles enter cells via lipidmediated endocytosis processes and interestingly, that the host membrane wrapping interactions depend on the length of the lipopolysaccharide macromolecules. Additional simulations were conducted to understand how polymyxin B1 peptides affect the inner and outer membranes of Gramnegative bacteria and how cohesive intermolecular interactions between lipopolysaccharide lipids can affect the durability of Gram-negative bacterial membranes. The simulation studies are by no means disparate; the simulations provide general insights into disease transmission. The simulations clarify how lipopolysaccharide macromolecules promote the spread of disease and conversely how antibiotics can curb it.
University of Southampton
Jefferies, Damien Francis
8df97e21-8df6-4571-bfbe-3edc41e16967
Jefferies, Damien Francis
8df97e21-8df6-4571-bfbe-3edc41e16967
Khalid, Syma
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Jefferies, Damien Francis (2019) Probing the molecular level details of bacterial outer membrane vesicles and their parent bacteria: A simulation approach. Doctoral Thesis, 367pp.

Record type: Thesis (Doctoral)

Abstract

Gram-negative bacteria have an unusual cell envelope that contains an inner cytoplasmic lipid membrane and an outer bacterial lipid membrane. The outer bacterial lipid membrane produces outer membrane vesicles that regulate bacterial pathogenesis processes. The outer membrane vesicles transport virulence factors from bacteria to host cell surfaces and the vesicles then move into the host cell cytosol. Computer simulations were conducted here in this thesis to understand how outer membrane vesicles pass through host cell surfaces independently of any membrane protein effects. The simulations suggest that outer membrane vesicles enter cells via lipidmediated endocytosis processes and interestingly, that the host membrane wrapping interactions depend on the length of the lipopolysaccharide macromolecules. Additional simulations were conducted to understand how polymyxin B1 peptides affect the inner and outer membranes of Gramnegative bacteria and how cohesive intermolecular interactions between lipopolysaccharide lipids can affect the durability of Gram-negative bacterial membranes. The simulation studies are by no means disparate; the simulations provide general insights into disease transmission. The simulations clarify how lipopolysaccharide macromolecules promote the spread of disease and conversely how antibiotics can curb it.

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Published date: September 2019

Identifiers

Local EPrints ID: 447133
URI: http://eprints.soton.ac.uk/id/eprint/447133
PURE UUID: 1b00d5a3-2454-4e7c-aa7f-f5109c3146d0
ORCID for Syma Khalid: ORCID iD orcid.org/0000-0002-3694-5044

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Date deposited: 03 Mar 2021 17:37
Last modified: 04 Mar 2021 02:39

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Contributors

Author: Damien Francis Jefferies
Thesis advisor: Syma Khalid ORCID iD

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