The bacterial outer membrane is found in
gram-negative bacteria
Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wall ...
. Its composition is distinct from that of the inner
cytoplasmic cell membrane - among other things, the outer leaflet of the outer membrane of many gram-negative bacteria includes a complex
lipopolysaccharide
Lipopolysaccharides (LPS) are large molecules consisting of a lipid and a polysaccharide that are bacterial toxins. They are composed of an O-antigen, an outer core, and an inner core all joined by a covalent bond, and are found in the outer ...
whose lipid portion acts as an
endotoxin
Lipopolysaccharides (LPS) are large molecules consisting of a lipid and a polysaccharide that are bacterial toxins. They are composed of an O-antigen, an outer core, and an inner core all joined by a covalent bond, and are found in the outer m ...
- and in some bacteria such as ''E. coli'' it is linked to the cell's
peptidoglycan
Peptidoglycan or murein is a unique large macromolecule, a polysaccharide, consisting of sugars and amino acids that forms a mesh-like peptidoglycan layer outside the plasma membrane, the rigid cell wall (murein sacculus) characteristic of most ba ...
by
Braun's lipoprotein
Braun's lipoprotein (BLP, Lpp, murein lipoprotein, or major outer membrane lipoprotein), found in some gram-negative cell walls, is one of the most abundant membrane proteins; its molecular weight is about 7.2 kDa. It is bound at its C-terminal en ...
.
Porins can be found in this layer.
Clinical significance
If
lipid A
Lipid A is a lipid component of an endotoxin held responsible for the toxicity of gram-negative bacteria. It is the innermost of the three regions of the lipopolysaccharide (LPS), also called endotoxin molecule, and its hydrophobic nature allows it ...
, part of the lipopolysaccharide, enters the
circulatory system
The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, tha ...
it causes a toxic reaction by activating
toll like receptor
Toll-like receptors (TLRs) are a class of proteins that play a key role in the innate immune system. They are single-pass membrane-spanning receptors usually expressed on sentinel cells such as macrophages and dendritic cells, that recognize s ...
TLR 4
Toll-like receptor 4 is a protein that in humans is encoded by the ''TLR4'' gene. TLR4 is a transmembrane protein, member of the toll-like receptor family, which belongs to the pattern recognition receptor (PRR) family. Its activation leads to an ...
. Lipid A is very pathogenic and not immunogenic. However, the polysaccharide component is very immunogenic, but not pathogenic, causing an aggressive response by the immune system. The sufferer will have a high temperature and respiration rate and a low blood pressure. This may lead to
endotoxic shock, which may be fatal. The bacterial outer membrane is physiologically shed as the bounding membrane of
outer membrane vesicles in cultures, as well as in animal tissues at the
host-pathogen interface, implicated in translocation of gram-negative microbial biochemical signals to host or target cells.
Biogenesis
The
biogenesis
Spontaneous generation is a superseded scientific theory that held that living creatures could arise from nonliving matter and that such processes were commonplace and regular. It was hypothesized that certain forms, such as fleas, could arise ...
of the outer membrane requires that the individual components are transported from the site of synthesis to their final destination outside the inner membrane by crossing both
hydrophilic
A hydrophile is a molecule or other molecular entity that is attracted to water molecules and tends to be dissolved by water.Liddell, H.G. & Scott, R. (1940). ''A Greek-English Lexicon'' Oxford: Clarendon Press.
In contrast, hydrophobes are ...
and
hydrophobic
In chemistry, hydrophobicity is the physical property of a molecule that is seemingly repelled from a mass of water (known as a hydrophobe). In contrast, hydrophiles are attracted to water.
Hydrophobic molecules tend to be nonpolar and, t ...
compartments. The machinery and the energy source that drive this process are not yet fully understood. The
lipid A
Lipid A is a lipid component of an endotoxin held responsible for the toxicity of gram-negative bacteria. It is the innermost of the three regions of the lipopolysaccharide (LPS), also called endotoxin molecule, and its hydrophobic nature allows it ...
-core moiety and the
O-antigen repeat units are synthesized at the
cytoplasm
In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. ...
ic face of the inner membrane and are separately exported via two independent transport systems, namely, the O-antigen transporter Wzx (RfbX) and the
ATP binding cassette (ABC) transporter MsbA that flips the lipid A-core moiety from the inner leaflet to the outer leaflet of the inner membrane.
O-antigen repeat units are then polymerised in the
periplasm
The periplasm is a concentrated gel-like matrix in the space between the inner cytoplasmic membrane and the bacterial outer membrane called the ''periplasmic space'' in gram-negative bacteria. Using cryo-electron microscopy it has been found that ...
by the Wzy
polymerase and ligated to the lipid A-core moiety by the WaaL
ligase
In biochemistry, a ligase is an enzyme that can catalyze the joining (ligation) of two large molecules by forming a new chemical bond. This is typically via hydrolysis of a small pendant chemical group on one of the larger molecules or the enzym ...
.
The
LPS transport machinery is composed of LptA, LptB, LptC, LptD, LptE. This supported by the fact that depletion of any one of these
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
s blocks the LPS assembly pathway and results in very similar outer membrane biogenesis defects. Moreover, the location of at least one of these five proteins in every
cellular compartment
Cellular compartments in cell biology comprise all of the closed parts within the cytosol of a eukaryotic cell, usually surrounded by a single or double lipid layer membrane. These compartments are often, but not always, defined as membrane-bo ...
suggests a model for how the LPS assembly pathway is organised and ordered in space.
LptC is required for the translocation of lipopolysaccharide (LPS) from the inner membrane to the outer membrane.
LptE forms a complex with LptD, which is involved in the assembly of LPS in the outer leaflet of the outer membrane and is essential for envelope biogenesis.
See also
*
Outer mitochondrial membrane
A mitochondrion (; ) is an organelle found in the cells of most Eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is use ...
*
Host-pathogen interface
References
{{InterPro content, IPR010664
Protein families
Membrane biology