Making a membrane on the other side of the wall

May, Kerrie L.; Silhavy, Thomas J.

doi:10.1016/j.bbalip.2016.10.004

Cited by 45 publications

(36 citation statements)

References 93 publications

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“…1 The outer membrane structure is unique, with an asymmetric lipid bilayer containing Lipopolysaccharide in the outer leaflet. 2 Furthermore, the trans-membrane proteins of the outer membrane are almost exclusively β-barrel in structure, compared to the strictly α-helical nature of proteins found in the inner membrane. Also, unlike most α-helical inner membrane proteins that fold co-translationally, outer membrane proteins (OMPs) fold post-translationally 3–6 .…”

mentioning

confidence: 99%

Extreme Dynamics in the BamA β-Barrel Seam

Doerner

Sousa

2017

Biochemistry

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BamA is an essential component of the β-barrel assembly machine (BAM) responsible for insertion and folding of β-barrel Outer Membrane Proteins (OMPs) in Gram negative bacteria. BamA is an OMP itself, and its β-barrel transmembrane domain is thought to catalyze OMP insertion and folding, although the molecular mechanism remains poorly understood. Crystal structures of BamA and complementary molecular dynamics simulations have shown that its β-barrel seam (the interface between the first and last barrel strands) is destabilized. This has led to mechanistic models where the BamA barrel seam functions as a lateral gate that opens and successively accepts β-hairpins from a nascent OMP such that a nascent barrel can bud from BamA. Consistent with this model, disulfide locking of the BamA barrel seam is lethal in E. coli. Here we show that disulfide locking of the BamA barrel has no effect on its ability to catalyze folding of a model OMP into liposomes. However, disulfide trapping experiments indicate that the BamA barrel is highly dynamic in the liposome membranes, with the β-strands at the barrel seam undergoing “register sliding” by more than 14Å both up and down the membrane. Remarkably, these extreme dynamics were also observed in the BamA barrel in the context of the native E. coli outer membrane. These results are consistent with a model where the BamA barrel dynamics induce defects in the outer membrane that facilitate insertion of nascent OMPs.

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confidence: 99%

Extreme Dynamics in the BamA β-Barrel Seam

Doerner

Sousa

2017

Biochemistry

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“…The OM of VBNC cells showed thick, convex patches reminiscent of the flagellar sheath. The asymmetric composition of the OM is tightly regulated to maintain its barrier function (see review [34]). Aberrations, such as the OM patches, might be symptomatic of a perturbed OM maintenance.…”

Section: Discussionmentioning

confidence: 99%

Structural and proteomic changes in viable but non-culturableVibrio cholerae

Brenzinger

Aart

Wezel

et al. 2018

Preprint

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Aquatic environments are reservoirs of the human pathogen Vibrio cholerae O1, which causes the acute diarrheal disease cholera. Upon low temperature or limited nutrient availability, the cells enter a viable but non-culturable (VBNC) state. Characteristic of this state are an altered morphology, low metabolic activity and lack of growth under standard laboratory conditions. Here, for the first time, the cellular ultrastructure of V. cholerae VBNC cells raised in natural waters was investigated using electron cryo-tomography complemented by comparison of the proteomes and the peptidoglycan composition of LB overnight culture and VBNC cells. The extensive remodeling of the VBNC cells was most obvious in the passive dehiscence of the cell envelope, resulting in improper embedment of flagella and pili. Only minor changes of the peptidoglycan and osmoregulated periplasmic glucans were observed. Active changes in VBNC cells included the production of cluster I chemosensory arrays and change of abundance of cluster II array proteins. Components involved in iron acquisition and storage, peptide import and arginine biosynthesis were overrepresented in VBNC cells, while enzymes of the central carbon metabolism were found at lower levels. Finally, several pathogenicity factors of V. cholerae were less abundant in the VBNC state, potentially limiting their infectious potential.

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“…Intimate structural synergy is now recognized between the peptidoglycan and the teichoic acids of the Gram‐positive bacteria, and between the peptidoglycan and the outer membrane of the Gram‐negative bacteria . Indeed, new opportunities for antibiotic discovery have been identified that interfere with teichoic acid integration into the cell wall of Gram‐positive bacteria and with respect to lipopolysaccharide transport in Gram‐negative bacteria . Within this universe of opportunity, we exemplify our own efforts toward the mechanistic and structural understanding of key enzymes of the bacteria with roles in cell envelope biosynthesis and antibiotic resistance.…”

Section: Cell Envelope‐targeting Antibioticsmentioning

confidence: 99%

“…77,78 Indeed, new opportunities for antibiotic discovery have been identified that interfere with teichoic acid integration into the cell wall of Gram-positive bacteria 69,[79][80][81][82][83][84] and with respect to lipopolysaccharide transport in Gram-negative bacteria. [85][86][87][88][89][90] Within this universe of opportunity, we exemplify our own efforts toward the mechanistic and structural understanding of key enzymes of the bacteria with roles in cell envelope biosynthesis and antibiotic resistance.…”

Section: Cell Envelope-targeting Antibioticsmentioning

confidence: 99%

Constructing and deconstructing the bacterial cell wall

Fisher

Mobashery

2019

Protein Science

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The history of modern medicine cannot be written apart from the history of the antibiotics. Antibiotics are cytotoxic secondary metabolites that are isolated from Nature. The antibacterial antibiotics disproportionately target bacterial protein structure that is distinct from eukaryotic protein structure, notably within the ribosome and within the pathways for bacterial cell‐wall biosynthesis (for which there is not a eukaryotic counterpart). This review focuses on a pre‐eminent class of antibiotics—the β‐lactams, exemplified by the penicillins and cephalosporins—from the perspective of the evolving mechanisms for bacterial resistance. The mechanism of action of the β‐lactams is bacterial cell‐wall destruction. In the monoderm (single membrane, Gram‐positive staining) pathogen Staphylococcus aureus the dominant resistance mechanism is expression of a β‐lactam‐unreactive transpeptidase enzyme that functions in cell‐wall construction. In the diderm (dual membrane, Gram‐negative staining) pathogen Pseudomonas aeruginosa a dominant resistance mechanism (among several) is expression of a hydrolytic enzyme that destroys the critical β‐lactam ring of the antibiotic. The key sensing mechanism used by P. aeruginosa is monitoring the molecular difference between cell‐wall construction and cell‐wall deconstruction. In both bacteria, the resistance pathways are manifested only when the bacteria detect the presence of β‐lactams. This review summarizes how the β‐lactams are sensed and how the resistance mechanisms are manifested, with the expectation that preventing these processes will be critical to future chemotherapeutic control of multidrug resistant bacteria.

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Making a membrane on the other side of the wall

Cited by 45 publications

References 93 publications

Extreme Dynamics in the BamA β-Barrel Seam

Extreme Dynamics in the BamA β-Barrel Seam

Structural and proteomic changes in viable but non-culturableVibrio cholerae

Constructing and deconstructing the bacterial cell wall

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