Structural Insights into Outer Membrane Permeability of Acinetobacter baumannii
Michael Zahn1, Satya Prathyusha Bhamidimarri2, Arnaud Baslé1
1Institute for Cellular and Molecular Biosciences, Medical School, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
Structure (London, England : 1993)
|January 26, 2016
Summary
Antibiotic resistance is a global threat. Understanding outer membrane (OM) channels in Gram-negative bacteria like Acinetobacter baumannii is key. Researchers characterized four OM carboxylate channel (Occ) proteins, identifying OccAB1 as a promising target for new antibiotic development.
Area of Science:
- Microbiology
- Structural Biology
- Drug Discovery
Background:
- Antibiotic resistance in Gram-negative bacteria is a significant global health challenge.
- The low permeability of the outer membrane (OM) in these bacteria is a primary mechanism of resistance.
- Outer membrane channel (OMC) proteins, specifically OM carboxylate channel (Occ) proteins in Acinetobacter baumannii, are crucial for small-molecule entry.
Purpose of the Study:
- To elucidate the structural and functional characteristics of Acinetobacter baumannii Occ proteins.
- To understand the role of Occ proteins in OM permeability and antibiotic resistance.
- To identify potential targets for novel antibiotic design.
Main Methods:
- X-ray crystallography was used to determine the structures of four Occ proteins (OccAB1-OccAB4).
- Biochemical and biophysical techniques, including electrophysiology and liposome swelling assays, were employed for characterization.
- Substrate specificities and channel properties were investigated.
Main Results:
- The X-ray crystal structures of four Occ proteins (OccAB1-OccAB4) were determined.
- OccAB1 was identified as possessing the largest pore among the studied Occ proteins.
- High rates of small-molecule uptake were observed through the OccAB1 channel, indicating significant permeability.
Conclusions:
- The structural and functional data provide critical insights into OM permeability in Acinetobacter baumannii.
- OccAB1 represents a key channel for small-molecule transport across the OM.
- Targeting the OccAB1 channel with specifically designed antibiotic scaffolds could overcome resistance mechanisms.
More Related Videos
05:06Author Spotlight: Advancing Antibiotic Resistance Research Using an Efflux-Deficient Bacterial Strain and a Single-Copy Gene Expression System
Published on: January 5, 2024
1.2K
08:37The Application of Open Searching-based Approaches for the Identification of Acinetobacter baumannii O-linked Glycopeptides
Published on: November 2, 2021
2.6K
Related Concept Videos
01:27Plasma Membrane in Bacteria and Archaea
2.9K
The plasma membrane is an essential cellular structure responsible for maintaining cellular integrity and regulating the selective transport of molecules. While bacteria and archaea share the fundamental function of plasma membranes, their structural and molecular differences reflect adaptations to distinct ecological and physiological challenges.Bacterial Plasma MembranesBacterial plasma membranes are predominantly composed of phospholipids with fatty acid chains ester-linked to a glycerol...
2.9K
01:21Structure of Porins
4.1K
Mitochondria, chloroplasts, and gram-negative bacteria have transmembrane, beta-barrel proteins called porins to mediate the free diffusion of ions and metabolites across the membrane. Mitochondrial porin precursors contain conserved amino acid sequences called beta signals at their C-terminal. Beta signals have a motif of PoXGXXHyXHy (Po-Polar, X-Any amino acid, G-Glycine, Hy-LargeHydrophobic), which are crucial for precursor recognition to initiate precursor assembly. Beta-barrel...
4.1K
01:25Mechanism of Antibiotic Resistance in MRSA
69
Antibiotic resistance in bacteria arises when microorganisms evolve the ability to withstand drugs designed to kill them or inhibit their growth, rendering once-effective treatments useless. This phenomenon, driven by genetic change and selection under antibiotic exposure, poses a profound threat to modern medicine. Mechanisms include drug-inactivating enzymes (e.g., β-lactamases), efflux pumps that eject antibiotics, mutations altering antibiotic targets, decreased drug uptake, and...
69
01:23Inhibitors of Gram-positive Cell Wall Synthesis
33
Bacterial cell walls are typically rigid structures composed mainly of peptidoglycan, a mesh-like polymer that provides mechanical strength and maintains cell shape. The synthesis of peptidoglycan is a crucial process in bacterial growth and serves as a primary target for many antibiotics.Mechanism of Action of Beta-Lactam AntibioticsBeta-lactam antibiotics, such as penicillin, inhibit peptidoglycan synthesis in actively growing cells. These antibiotics share a characteristic four-membered...
33
01:22Bacterial Cell Wall
5.2K
The bacterial cell wall is an essential structural component that encases the plasma membrane, preserving cellular integrity, determining shape, and protecting against osmotic stress. This rigid yet flexible structure primarily comprises peptidoglycan, a polymer that forms a mesh-like matrix conferring mechanical strength and flexibility.Peptidoglycan Composition and StructurePeptidoglycan, the core of the bacterial cell wall, comprises alternating units of N-acetylglucosamine (NAG) and...
5.2K
01:18Outer Layers of the Cell Envelope
1.5K
The outermost layers of prokaryotic cells play a critical role in their survival, virulence, and interaction with the environment. These layers, often composed of polysaccharides, polypeptides, or proteins, form protective and adhesive structures that vary in organization and function.Capsules and Slime LayersCapsules are highly organized, tightly bound layers that firmly attach to the bacterial cell wall. Capsules are usually made of polysaccharides, though some are made of polypeptides. These...
1.5K