Outer Membrane Vesicles
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Outer membrane vesicles (OMVs) are
vesicles Vesicle may refer to: ; In cellular biology or chemistry * Vesicle (biology and chemistry), a supramolecular assembly of lipid molecules, like a cell membrane * Synaptic vesicle ; In human embryology * Vesicle (embryology), bulge-like features o ...
released from the outer membranes of
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 ...
. While
Gram-positive bacteria In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. Gram-positive bact ...
release vesicles as well, those vesicles fall under the broader category of bacterial membrane vesicles (MVs). OMVs were the first MVs to be discovered, and are distinguished from outer inner membrane vesicles (OIMVs), which are gram-negative bacterial vesicles containing portions of both the outer and inner bacterial membrane. Outer membrane vesicles were first discovered and characterized using transmission-electron microscopy by
Indian Indian or Indians may refer to: Peoples South Asia * Indian people, people of Indian nationality, or people who have an Indian ancestor ** Non-resident Indian, a citizen of India who has temporarily emigrated to another country * South Asia ...
Scientist Prof. Smriti Narayan Chatterjee and J. Das in 1966-67. OMVs are ascribed the functionality to provide a manner to communicate among themselves, with other
microorganism A microorganism, or microbe,, ''mikros'', "small") and ''organism'' from the el, ὀργανισμός, ''organismós'', "organism"). It is usually written as a single word but is sometimes hyphenated (''micro-organism''), especially in olde ...
s in their environment and with the host. These vesicles are involved in
trafficking Smuggling is the illegal transportation of objects, substances, information or people, such as out of a house or buildings, into a prison, or across an international border, in violation of applicable laws or other regulations. There are various ...
bacterial
cell signaling In biology, cell signaling (cell signalling in British English) or cell communication is the ability of a cell to receive, process, and transmit signals with its environment and with itself. Cell signaling is a fundamental property of all cellula ...
biochemicals, which may include DNA,
RNA Ribonucleic acid (RNA) is a polymeric molecule essential in various biological roles in coding, decoding, regulation and expression of genes. RNA and deoxyribonucleic acid ( DNA) are nucleic acids. Along with lipids, proteins, and carbohydra ...
,
proteins 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, respo ...
,
endotoxins 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 me ...
and allied
virulence Virulence is a pathogen's or microorganism's ability to cause damage to a host. In most, especially in animal systems, virulence refers to the degree of damage caused by a microbe to its host. The pathogenicity of an organism—its ability to ca ...
molecules. This communication happens in
microbial culture A microbiological culture, or microbial culture, is a method of multiplying microbial organisms by letting them reproduce in predetermined culture medium under controlled laboratory conditions. Microbial cultures are foundational and basic diagn ...
s in oceans, inside animals, plants and even inside the human body. Gram-negative bacteria deploy their
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 ...
to secrete OMVs for trafficking bacterial biochemicals to target cells in their environment. OMVs also can carry endotoxic
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 m ...
that may contribute to disease processes in their host. This mechanism imparts a variety of benefits like, long-distance delivery of bacterial secretory cargo with minimized hydrolytic degradation and extra-cellular dilution, also supplemented with other supportive molecules (e.g., virulence factors) to accomplish a specific job and yet, keeping a safe-distance from the defense arsenal of the targeted cells. Biochemical signals trafficked by OMVs may vary largely during 'war and peace' situations. In 'complacent' bacterial colonies, OMVs may be used to carry DNA to 'related' microbes for genetic transformations, and also translocate
cell signaling In biology, cell signaling (cell signalling in British English) or cell communication is the ability of a cell to receive, process, and transmit signals with its environment and with itself. Cell signaling is a fundamental property of all cellula ...
molecules for
quorum sensing In biology, quorum sensing or quorum signalling (QS) is the ability to detect and respond to cell population density by gene regulation. As one example, QS enables bacteria to restrict the expression of specific genes to the high cell densities at ...
and
biofilm A biofilm comprises any syntrophic consortium of microorganisms in which cells stick to each other and often also to a surface. These adherent cells become embedded within a slimy extracellular matrix that is composed of extracellular ...
formation. During 'challenge' from other cell types around, OMVs may be preferred to carry degradation and subversion enzymes. Likewise, OMVs may contain more of invasion proteins at the host–pathogen interface (Fig. 1). It is expected that environmental factors around the secretory microbes are responsible for inducing these bacteria to synthesize and secrete specifically-enriched OMVs, physiologically suiting the immediate task. Thus, bacterial OMVs, being strong
immunomodulator Immunotherapy or biological therapy is the treatment of disease by activating or suppressing the immune system. Immunotherapies designed to elicit or amplify an immune response are classified as ''activation immunotherapies,'' while immunotherap ...
s, can be manipulated for their
immunogenic Immunogenicity is the ability of a foreign substance, such as an antigen, to provoke an immune response in the body of a human or other animal. It may be wanted or unwanted: * Wanted immunogenicity typically relates to vaccines, where the injectio ...
contents and utilized as potent
pathogen In biology, a pathogen ( el, πάθος, "suffering", "passion" and , "producer of") in the oldest and broadest sense, is any organism or agent that can produce disease. A pathogen may also be referred to as an infectious agent, or simply a germ ...
-free
vaccines A vaccine is a biological preparation that provides active acquired immunity The adaptive immune system, also known as the acquired immune system, is a subsystem of the immune system that is composed of specialized, systemic cells and pro ...
for immunizing humans and animals against threatening
infection An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dise ...
s. VA-MENGOC-BC and Bexsero against
meningitis Meningitis is acute or chronic inflammation of the protective membranes covering the brain and spinal cord, collectively called the meninges. The most common symptoms are fever, headache, and neck stiffness. Other symptoms include confusion or ...
are currently the only OMV vaccines approved in the US, though an OMV vaccine for
gonorrhea Gonorrhea, colloquially known as the clap, is a sexually transmitted infection (STI) caused by the bacterium '' Neisseria gonorrhoeae''. Infection may involve the genitals, mouth, or rectum. Infected men may experience pain or burning with ...
is seeking approval.


Biogenesis and movement

Gram-negative bacteria have a double set of
lipid bilayer The lipid bilayer (or phospholipid bilayer) is a thin polar membrane made of two layers of lipid molecules. These membranes are flat sheets that form a continuous barrier around all cells. The cell membranes of almost all organisms and many vir ...
s. An inner bilayer, the inner
cell membrane The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...
, encloses 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. The ...
or
cytosol The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells (intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondri ...
. Surrounding this inner cell membrane there is a second bilayer called the
bacterial outer membrane The bacterial outer membrane is found in gram-negative bacteria. 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 ...
. The compartment or space between these two membranes is called 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 ...
or
periplasmic space 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 ...
. In addition, there is a firm
cell wall A cell wall is a structural layer surrounding some types of cells, just outside the cell membrane. It can be tough, flexible, and sometimes rigid. It provides the cell with both structural support and protection, and also acts as a filtering mech ...
consisting of
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 ...
layer, which surrounds the cell membrane and occupies the periplasmic space. The peptidoglycan layer provides some rigidity for maintaining the bacterial cell shape, besides also protecting the microbe against challenging environments. The first step in
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 fr ...
of gram-negative bacterial OMVs, is ''bulging'' of outer membrane above the peptidoglycan layer. Accumulation of phospholipids in the outside of the outer membrane is thought to be the basis of this outwards bulging of the outer membrane. This accumulation of phospholipids can be regulated by the VacJ/Yrb ABC transport system that transfers phospholipids from the outside of OM to the inner side. Additionally, environmental conditions as sulfur depletion can trigger a state of phospholipid overproduction that causes increased OMV release. The actual release of the vesicle from the outer membrane remains unclear. It is likely that vesicle structures can be released spontaneously. Alternatively, it has been suggested that few proteins 'rivet' the outer and cell membranes together, so that the periplasmic bulge protrudes like a 'ballooned' pocket of inflated periplasm out from the surface of the outer membrane. Lateral diffusion of 'rivet complexes' may help in pinching off large bulges of periplasm as OMVs. Bacterial membrane vesicles' dispersion along the cell surface was measured in live ''
Escherichia coli ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus ''Escher ...
'', commensal bacteria common in the human gut. Antibiotic treatment altered vesicle dynamics, vesicle-to-membrane affinity, and surface properties of the cell membranes, generally enhancing vesicle transport along the surfaces of bacterial membranes and suggesting that their motion properties could be a signature of antibiotic stress. Despite this first high-resolution, quantitative tracking of bacterial OMVs, detailed experimental work is still awaited to understand the
biomechanics Biomechanics is the study of the structure, function and motion of the mechanical aspects of biological systems, at any level from whole organisms to organs, cells and cell organelles, using the methods of mechanics. Biomechanics is a branch of ...
of OMV biogenesis and transport. OMVs are also under focus of current research in
exocytosis Exocytosis () is a form of active transport and bulk transport in which a cell transports molecules (e.g., neurotransmitters and proteins) out of the cell ('' exo-'' + ''cytosis''). As an active transport mechanism, exocytosis requires the use o ...
in
prokaryotes A prokaryote () is a single-celled organism that lacks a nucleus and other membrane-bound organelles. The word ''prokaryote'' comes from the Greek πρό (, 'before') and κάρυον (, 'nut' or 'kernel').Campbell, N. "Biology:Concepts & Connec ...
via outer
membrane vesicle trafficking Membrane vesicle trafficking in eukaryotic animal cells involves movement of biochemical signal molecules from synthesis-and-packaging locations in the Golgi body to specific release locations on the inside of the plasma membrane of the secretory c ...
for intra-species, inter-species and inter-kingdom
cell signaling In biology, cell signaling (cell signalling in British English) or cell communication is the ability of a cell to receive, process, and transmit signals with its environment and with itself. Cell signaling is a fundamental property of all cellula ...
, which is slated to change our mindset on
virulence Virulence is a pathogen's or microorganism's ability to cause damage to a host. In most, especially in animal systems, virulence refers to the degree of damage caused by a microbe to its host. The pathogenicity of an organism—its ability to ca ...
of microbes,
host–pathogen interaction The host–pathogen interaction is defined as how microbes or viruses sustain themselves within host organisms on a molecular, cellular, organismal or population level. This term is most commonly used to refer to disease-causing microorganisms alt ...
s and inter-relationships among variety of species in earth's
ecosystem An ecosystem (or ecological system) consists of all the organisms and the physical environment with which they interact. These biotic and abiotic components are linked together through nutrient cycles and energy flows. Energy enters the syste ...
.


See also

*
Exocytosis Exocytosis () is a form of active transport and bulk transport in which a cell transports molecules (e.g., neurotransmitters and proteins) out of the cell ('' exo-'' + ''cytosis''). As an active transport mechanism, exocytosis requires the use o ...
*
Host–pathogen interaction The host–pathogen interaction is defined as how microbes or viruses sustain themselves within host organisms on a molecular, cellular, organismal or population level. This term is most commonly used to refer to disease-causing microorganisms alt ...
s * Host–pathogen interface *
List of bacterial disulfide oxidoreductases Bacterial thiol disulfide oxidoreductases (TDOR) are bacterial enzymes which, along with unfolded proteins, are Secretory pathway, pumped out of a bacterial cell that allow for adhesion and biofilm development, and generally disease development. T ...
*
Virulence Virulence is a pathogen's or microorganism's ability to cause damage to a host. In most, especially in animal systems, virulence refers to the degree of damage caused by a microbe to its host. The pathogenicity of an organism—its ability to ca ...


References

{{reflist Bacteriology Membrane biology Prokaryotic cell anatomy