scholarly journals Structure and inhibition of enzymes that assemble outer membrane lipids

2006 ◽  
Vol 20 (5) ◽  
Author(s):  
Christian R.H. Raetz
Keyword(s):  
Outer Membrane ◽  
Membrane Lipids

scholarly journals Interaction of quorum signals with outer membrane lipids: insights into prokaryotic membrane vesicle formation

2008 ◽  
Vol 69 (2) ◽  
pp. 491-502 ◽  
Author(s):  
Lauren Mashburn-Warren ◽  
Jörg Howe ◽  
Patrick Garidel ◽  
Walter Richter ◽  
Frank Steiniger ◽  
...  
Keyword(s):  
Outer Membrane ◽  
Membrane Lipids ◽  
Membrane Vesicle ◽  
Vesicle Formation

scholarly journals Lipid Headgroup Charge and Acyl Chain Composition Modulate Closure of Bacterial β-Barrel Channels

2019 ◽  
Vol 20 (3) ◽  
pp. 674 ◽  
Author(s):  
D. Perini ◽  
Antonio Alcaraz ◽  
María Queralt-Martín
Keyword(s):  
Membrane Permeability ◽  
Outer Membrane ◽  
Protein Interactions ◽  
Membrane Lipids ◽  
Acyl Chain ◽  
Extensive Study ◽  
Electrophysiological Recordings ◽  
Sequential Closure ◽  
Lipid Protein Interactions ◽  
Outer Membrane Permeability

The outer membrane of Gram-negative bacteria contains β-barrel proteins that form high-conducting ion channels providing a path for hydrophilic molecules, including antibiotics. Traditionally, these proteins have been considered to exist only in an open state so that regulation of outer membrane permeability was accomplished via protein expression. However, electrophysiological recordings show that β-barrel channels respond to transmembrane voltages by characteristically switching from a high-conducting, open state, to a so-called ‘closed’ state, with reduced permeability and possibly exclusion of large metabolites. Here, we use the bacterial porin OmpF from E. coli as a model system to gain insight on the control of outer membrane permeability by bacterial porins through the modulation of their open state. Using planar bilayer electrophysiology, we perform an extensive study of the role of membrane lipids in the OmpF channel closure by voltage. We pay attention not only to the effects of charges in the hydrophilic lipid heads but also to the contribution of the hydrophobic tails in the lipid-protein interactions. Our results show that gating kinetics is governed by lipid characteristics so that each stage of a sequential closure is different from the previous one, probably because of intra- or intermonomeric rearrangements.

scholarly journals SalmonellaTol-Pal Reduces Outer Membrane Glycerophospholipid Levels for Envelope Homeostasis and Survival during Bacteremia

2018 ◽  
Vol 86 (7) ◽  
Author(s):  
Revathi Masilamani ◽  
Melina B. Cian ◽  
Zachary D. Dalebroux
Keyword(s):  
Outer Membrane ◽  
Membrane Lipids ◽  
Lipid Homeostasis ◽  
Content Type ◽  
Bacterial Morphology ◽  
Serovar Typhimurium ◽  
Genes Encoding ◽  
Rifampin Resistance ◽  
Mutant Phenotypes ◽  
Acyl Coenzyme A

ABSTRACTSalmonellae regulate membrane lipids during infection, but the exact proteins and mechanisms that promote their survival during bacteremia remain largely unknown. Mutations in genes encoding the conservedSalmonella entericaserovar Typhimurium (S. Typhimurium) Tol-Pal apparatus caused the outer membrane (OM) sensor lipoprotein, RcsF, to become activated. The capsule activation phenotype for the mutants suggested that Tol-Pal might influence envelope lipid homeostasis. The mechanism involves reducing OM glycerophospholipid (GPL) levels, since the mutant salmonellae similarly accumulated phosphatidylglycerols (PGl) and phosphatidylethanolamines (PE) within the OM in comparison to the wild type. The data support theEscherichia colimodel, whereby Tol-Pal directs retrograde GPL translocation across the periplasm. TheS. Typhimurium mechanism involves contributions from YbgC, a cytoplasmic acyl coenzyme A (acyl-CoA) thioesterase, and CpoB, a periplasmic TolA-binding protein. The functional relationship between Tol-Pal and YbgC and CpoB was previously unresolved. TheS. Typhimurium Tol-Pal proteins contribute similarly toward promoting OM-GPL homeostasis and Rcs signaling inactivity but differently toward promoting bacterial morphology, rifampin resistance, survival in macrophages, and survival in mice. For example,tolQ,tolR,tolA, andcpoBmutants were significantly more attenuated thanybgC,tolB, andpalmutants in a systemic mouse model of disease. Therefore, key roles exist for TolQ, TolR, TolA, and CpoB during murine bacteremia, which are independent of maintaining GPL homeostasis. The ability of TolQR to channel protons across the inner membrane (IM) is necessary forS. Typhimurium TolQRA function, since mutating conserved channel-facing residues rendered TolQ ineffective at rescuing deletion mutant phenotypes. Therefore, Tol-Pal promotesS. Typhimurium survival during bacteremia, in part, by reducing OM GPL concentrations, while TolQRA and CpoB enhance systemic virulence by additional mechanisms.

scholarly journals Dynamical Organization of Compositionally Distinct Inner and Outer Membrane Lipids of Mycobacteria

2020 ◽  
Vol 118 (6) ◽  
pp. 1279-1291 ◽  
Author(s):  
Pranav Adhyapak ◽  
Aswin T. Srivatsav ◽  
Manjari Mishra ◽  
Abhishek Singh ◽  
Rishikesh Narayan ◽  
...  
Keyword(s):  
Outer Membrane ◽  
Membrane Lipids

scholarly journals Prediction of the closed conformation and insights into the mechanism of the membrane enzyme LpxR

2018 ◽  
Author(s):  
Graham M Saunders ◽  
Hannah E Bruce Macdonald ◽  
Jonathan W Essex ◽  
Syma Khalid
Keyword(s):  
Outer Membrane ◽  
Membrane Lipids ◽  
Conformational Dynamics ◽  
Covalent Modification ◽  
Conserved Residues ◽  
Free Binding Energy ◽  
Scissile Bond ◽  
Membrane Models ◽  
Single Water Molecule ◽  
Key Residues

ABSTRACTCovalent modification of outer membrane lipids of Gram-negative bacteria can impact the ability of the bacterium to develop resistance to antibiotics as well as modulating the immune response of the host. The enzyme LpxR from Salmonella typhimurium is known to deacylate lipopolysaccharide molecules of the outer membrane, however the mechanism of action is unknown. Here we employ Molecular Dynamics and Monte Carlo simulations to study the conformational dynamics and substrate binding of LpxR in representative outer membrane models and also detergent micelles. We examine the roles of conserved residues and provide an understanding of how LpxR binds its substrate. Our simulations predict that the catalytic H122 must be Nε-protonated for a single water molecule to occupy the space between it and the scissile bond, with a free binding energy of -8.5 kcal mol-1. Furthermore, simulations of the protein within a micelle enable us to predict the structure of the putative ‘closed’ protein. Our results highlight the need for including dynamics, a representative environment and the consideration of multiple tautomeric and rotameric states of key residues in mechanistic studies; static structures alone do not tell the full story.

Modeling Diversity in Structures of Bacterial Outer Membrane Lipids

2017 ◽  
Vol 13 (2) ◽  
pp. 811-824 ◽  
Author(s):  
Huilin Ma ◽  
Daniel D. Cummins ◽  
Natalie Brooke Edelstein ◽  
Jerry Gomez ◽  
Aliza Khan ◽  
...  
Keyword(s):  
Outer Membrane ◽  
Membrane Lipids ◽  
Bacterial Outer Membrane

Transport of outer membrane lipids in mycobacteria

2017 ◽  
Vol 1862 (11) ◽  
pp. 1340-1354 ◽  
Author(s):  
Megan H. Touchette ◽  
Jessica C. Seeliger
Keyword(s):  
Outer Membrane ◽  
Membrane Lipids

scholarly journals Mycobacterial Virulence Factors: Surface-Exposed Lipids and Secreted Proteins

2020 ◽  
Vol 21 (11) ◽  
pp. 3985 ◽  
Author(s):  
Angel Ly ◽  
Jun Liu
Keyword(s):  
Outer Membrane ◽  
Virulence Factors ◽  
Structural Model ◽  
Membrane Lipids ◽  
Secretion Systems ◽  
Type Vii Secretion ◽  
System 1 ◽  
Phthiocerol Dimycocerosates ◽  
Insight Into ◽  
Phenolic Glycolipids

The clinically important Mycobacterium tuberculosis (M. tb) and related mycobacterial pathogens use various virulence mechanisms to survive and cause disease in their hosts. Several well-established virulence factors include the surface-exposed lipids in the mycobacterial outer membrane, as well as the Esx family proteins and the Pro-Glu (PE)/ Pro-Pro-Glu (PPE) family proteins secreted by type VII secretion systems (T7SS). Five ESX T7SS exist in M. tb and three—EsxA secretion system-1 (ESX-1), ESX-3, and ESX-5—have been implicated in virulence, yet only the structures of ESX-3 and ESX-5 have been solved to date. Here, we summarize the current research on three outer membrane lipids—phthiocerol dimycocerosates, phenolic glycolipids, and sulfolipids—as well as the secretion machinery and substrates of three mycobacterial T7SS—ESX-1, ESX-3, and ESX-5. We propose a structural model of the M. tb ESX-1 system based on the latest structural findings of the ESX-3 and ESX-5 secretion apparatuses to gain insight into the transport mechanism of ESX-associated virulence factors.

Sign in / Sign up

Export Citation Format

Share Document