Surfactin
Encyclopedia
Surfactin is a very powerful surfactant
commonly used as an antibiotic
. It is a bacteria
l cyclic
lipopeptide
, largely prominent for its exceptional surfactant power. Its amphiphilic properties help this substance to survive in both hydrophilic and hydrophobic environments. It is one of the 24 types of antibiotics produced by the Gram-positive
endospore
-forming bacteria Bacillus subtilis
. In the course of various studies of its properties, surfactin was found to exhibit effective characteristics like anti-bacterial, anti-viral
, anti-fungal, anti-mycoplasma
and hemolytic activities.
loop of seven amino acids (L-asparagine
, L-leucine
, glutamic acid
, L-leucine, L-valine
and two D-leucines), and a hydrophobic fatty acid
chain thirteen to fifteen carbon
s long which allows its ability to penetrate cellular membranes
. Glutamic acid and asparagine residues at positions 1 and 5 respectively, constituting a minor polar domain. On the opposite side, valine residue at position 4 extends down facing the fatty acid chain, making up a major hydrophobic domain. Below critical micellar concentrations (CMCs) the fatty acid tail can extend freely into solution
, and then participate in hydrophobic interactions within micelles. This antibiotic is synthesized by a linear nonribosomal peptide
synthetase, surfactin synthetase, and has, in solution, a characteristic "horse saddle" conformation
that explains its large spectrum of biological activity.
's surface tension
from 72 mN/m to 27 mN/m at a concentration as low as 20 µM. Surfactin accomplishes this effect as it occupies the intermolecular space between water molecule
s, decreasing the attractive forces between adjacent water molecules, mainly hydrogen bond
s, creating a more fluid
solution that can go into tighter regions of space increasing water’s wetting ability. Overall, this property is significant not only for surfactin but for surfactants as a whole, as they are primarily used as detergents and soap
s.
and divalent
cations through an organic
barrier. The two acid
ic residues asparagine and glycine form a "claw" of sorts which easily stabilizes divalent cations. Calcium
ions make for the best-fitting cations stabilizing the surfactin conformation and functioning as an assembly template for the formation of micelles. When surfactin penetrates the outer sheet, its fatty acid chain interacts with the acyl
chains of the phospholipid
s, with its headgroup in proximity to the phospholipids polar heads. Attachment of a cation to causes the complex to cross the bilipidic layer undergoing a flip-flop
. The headgroup aligns itself with the phospholipids of the inner sheet and the fatty acid chain interacts with the phospholipids acyl chains. The cation is then delivered into the intracellular medium.
) effect is characterized by the formation of cationic channels. It would require surfactin to self-associate inside the membrane, since it cannot span across the cellular membrane. Supramolecular-like structures by successive self-association
could then form a channel. This hypothesis for the most part applies only to uncharged membranes where there is a minimal energy barrier between outer and inner membrane leaflets.
. Consequently, this efficient mode of cell destruction is indiscriminate, and attacks red blood cells with deadly efficiency.
and Gram-positive. The two bacteria types differ in the composition of their membrane. The Gram-negative bacteria have an outer lipopolysaccharide
membrane and a thin peptidoglycan layer followed by a phospholipids bilayer, whereas the Gram-positive bacteria lack the outer membrane and carry a thicker peptidoglycan
layer as well as a phospholipids bilayer. This is an essential factor that contributes to surfactin’s detergent-like activity as it is able to create a permeable environment for the lipid bilayer and causes disruption that solubilizes the membrane.
For surfactin to carry out its antibacterial property successfully, the bacterium needs to be treated with a high concentration. In fact, surfactin needs to be in concentrations between 12–50 µg
/ml
in order for it to carry out minimal antibacterial effects. This is also known as the minimum inhibitory concentration (MIC).
The antiviral effects of surfactin distinguish this antibiotic from others. This property is such because surfactin has been found to disintegrate enveloped virus
es. Surfactin not only disintegrates the viral lipid enveloped, but also the capsid
of the virus through ion channel formations. This process has been proven through test on several envelop viruses such as HIV
and HSV
. Also, the isoforms of the fatty acid chain containing 14 or 15 carbon atoms exhibited an improvement in inactivation of the viral envelops. Unfortunately, surfactin only affected cell-free viruses and those that had penetrated the cell were unaffected. Concurrently, if surfactin were exposed to a high medium of protein or lipid concentrations, its antiviral activity would be limited. This is also known as the buffer effect and is a significant drawback in surfactin’s antiviral activity.
a cell. The hemolytic effect has been the result of surfactin having the ability to lyse red blood cells that is enough to warrant caution if used intravascularly. Fortunately, these results were seen at high concentrations of about 40 µM to 60 µM. These concentrations also exhibited the effect of proliferating cells in vitro though it also was the for this type of cells. At concentrations below 25 µM, toxicity effects of surfactin are not significant.
Surfactant
Surfactants are compounds that lower the surface tension of a liquid, the interfacial tension between two liquids, or that between a liquid and a solid...
commonly used as an antibiotic
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
. It is a bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...
l cyclic
Cyclic compound
In chemistry, a cyclic compound is a compound in which a series of atoms is connected to form a loop or ring.While the vast majority of cyclic compounds are organic, a few inorganic substances form cyclic compounds as well, including sulfur, silanes, phosphanes, phosphoric acid, and triboric acid. ...
lipopeptide
Lipopeptide
A lipopeptide is a molecule consisting of a lipid connected to a peptide. Bacteria express these molecules. They are bound by TLR 1, and other, Toll-like receptors.Certain lipopeptides are used as antibiotics....
, largely prominent for its exceptional surfactant power. Its amphiphilic properties help this substance to survive in both hydrophilic and hydrophobic environments. It is one of the 24 types of antibiotics produced by the Gram-positive
Gram-positive
Gram-positive bacteria are those that are stained dark blue or violet by Gram staining. This is in contrast to Gram-negative bacteria, which cannot retain the crystal violet stain, instead taking up the counterstain and appearing red or pink...
endospore
Endospore
An endospore is a dormant, tough, and temporarily non-reproductive structure produced by certain bacteria from the Firmicute phylum. The name "endospore" is suggestive of a spore or seed-like form , but it is not a true spore . It is a stripped-down, dormant form to which the bacterium can reduce...
-forming bacteria Bacillus subtilis
Bacillus subtilis
Bacillus subtilis, known also as the hay bacillus or grass bacillus, is a Gram-positive, catalase-positive bacterium commonly found in soil. A member of the genus Bacillus, B. subtilis is rod-shaped, and has the ability to form a tough, protective endospore, allowing the organism to tolerate...
. In the course of various studies of its properties, surfactin was found to exhibit effective characteristics like anti-bacterial, anti-viral
Antiviral drug
Antiviral drugs are a class of medication used specifically for treating viral infections. Like antibiotics for bacteria, specific antivirals are used for specific viruses...
, anti-fungal, anti-mycoplasma
Mycoplasma
Mycoplasma refers to a genus of bacteria that lack a cell wall. Without a cell wall, they are unaffected by many common antibiotics such as penicillin or other beta-lactam antibiotics that target cell wall synthesis. They can be parasitic or saprotrophic. Several species are pathogenic in humans,...
and hemolytic activities.
Structure and Synthesis
Surfactin's structure consists of a peptidePeptide
Peptides are short polymers of amino acid monomers linked by peptide bonds. They are distinguished from proteins on the basis of size, typically containing less than 50 monomer units. The shortest peptides are dipeptides, consisting of two amino acids joined by a single peptide bond...
loop of seven amino acids (L-asparagine
Asparagine
Asparagine is one of the 20 most common natural amino acids on Earth. It has carboxamide as the side-chain's functional group. It is not an essential amino acid...
, L-leucine
Leucine
Leucine is a branched-chain α-amino acid with the chemical formula HO2CCHCH2CH2. Leucine is classified as a hydrophobic amino acid due to its aliphatic isobutyl side chain. It is encoded by six codons and is a major component of the subunits in ferritin, astacin and other 'buffer' proteins...
, glutamic acid
Glutamic acid
Glutamic acid is one of the 20 proteinogenic amino acids, and its codons are GAA and GAG. It is a non-essential amino acid. The carboxylate anions and salts of glutamic acid are known as glutamates...
, L-leucine, L-valine
Valine
Valine is an α-amino acid with the chemical formula HO2CCHCH2. L-Valine is one of 20 proteinogenic amino acids. Its codons are GUU, GUC, GUA, and GUG. This essential amino acid is classified as nonpolar...
and two D-leucines), and a hydrophobic fatty acid
Fatty acid
In chemistry, especially biochemistry, a fatty acid is a carboxylic acid with a long unbranched aliphatic tail , which is either saturated or unsaturated. Most naturally occurring fatty acids have a chain of an even number of carbon atoms, from 4 to 28. Fatty acids are usually derived from...
chain thirteen to fifteen carbon
Carbon
Carbon is the chemical element with symbol C and atomic number 6. As a member of group 14 on the periodic table, it is nonmetallic and tetravalent—making four electrons available to form covalent chemical bonds...
s long which allows its ability to penetrate cellular membranes
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...
. Glutamic acid and asparagine residues at positions 1 and 5 respectively, constituting a minor polar domain. On the opposite side, valine residue at position 4 extends down facing the fatty acid chain, making up a major hydrophobic domain. Below critical micellar concentrations (CMCs) the fatty acid tail can extend freely into solution
Solution
In chemistry, a solution is a homogeneous mixture composed of only one phase. In such a mixture, a solute is dissolved in another substance, known as a solvent. The solvent does the dissolving.- Types of solutions :...
, and then participate in hydrophobic interactions within micelles. This antibiotic is synthesized by a linear nonribosomal peptide
Nonribosomal peptide
Nonribosomal peptides are a class of peptide secondary metabolites, usually produced by microorganisms like bacteria and fungi. Nonribosomal peptides are also found in higher organisms, such as nudibranchs, but are thought to be made by bacteria inside these organisms...
synthetase, surfactin synthetase, and has, in solution, a characteristic "horse saddle" conformation
Chemical structure
A chemical structure includes molecular geometry, electronic structure and crystal structure of molecules. Molecular geometry refers to the spatial arrangement of atoms in a molecule and the chemical bonds that hold the atoms together. Molecular geometry can range from the very simple, such as...
that explains its large spectrum of biological activity.
Surface tension
Surfactin, like other surfactants, affects the surface tension of liquids in which it is dissolved. It can lower the waterWater
Water is a chemical substance with the chemical formula H2O. A water molecule contains one oxygen and two hydrogen atoms connected by covalent bonds. Water is a liquid at ambient conditions, but it often co-exists on Earth with its solid state, ice, and gaseous state . Water also exists in a...
's surface tension
Surface tension
Surface tension is a property of the surface of a liquid that allows it to resist an external force. It is revealed, for example, in floating of some objects on the surface of water, even though they are denser than water, and in the ability of some insects to run on the water surface...
from 72 mN/m to 27 mN/m at a concentration as low as 20 µM. Surfactin accomplishes this effect as it occupies the intermolecular space between water molecule
Molecule
A molecule is an electrically neutral group of at least two atoms held together by covalent chemical bonds. Molecules are distinguished from ions by their electrical charge...
s, decreasing the attractive forces between adjacent water molecules, mainly hydrogen bond
Hydrogen bond
A hydrogen bond is the attractive interaction of a hydrogen atom with an electronegative atom, such as nitrogen, oxygen or fluorine, that comes from another molecule or chemical group. The hydrogen must be covalently bonded to another electronegative atom to create the bond...
s, creating a more fluid
Fluidity
Fluidity may refer toIn science*reciprocal of viscosity*Cognitive fluidity*Membrane fluidity*Sexual fluidityOthers*Fluidity *Dark Fluidity – a literature magazine*Empire Fane ship...
solution that can go into tighter regions of space increasing water’s wetting ability. Overall, this property is significant not only for surfactin but for surfactants as a whole, as they are primarily used as detergents and soap
Soap
In chemistry, soap is a salt of a fatty acid.IUPAC. "" Compendium of Chemical Terminology, 2nd ed. . Compiled by A. D. McNaught and A. Wilkinson. Blackwell Scientific Publications, Oxford . XML on-line corrected version: created by M. Nic, J. Jirat, B. Kosata; updates compiled by A. Jenkins. ISBN...
s.
Molecular mechanisms
There are three prevailing hypotheses for how surfactin works. These are described below.Cation-carrier effect
The cation-carrier effect is characterized by surfactin’s ability to drive monovalentMonovalent
Monovalent may refer to:*In chemistry, valence is a measure of the number of chemical bonds formed by the atoms of a given element. Monovalent is a synonym of univalent.*Monovalent ions contain one valence electron....
and divalent
Divalent
In chemistry, a divalent ion or molecule has a valence of two and thus can form two bonds with other ions or molecules. An older term for divalent is bivalent....
cations through an organic
Organic compound
An organic compound is any member of a large class of gaseous, liquid, or solid chemical compounds whose molecules contain carbon. For historical reasons discussed below, a few types of carbon-containing compounds such as carbides, carbonates, simple oxides of carbon, and cyanides, as well as the...
barrier. The two acid
Acid
An acid is a substance which reacts with a base. Commonly, acids can be identified as tasting sour, reacting with metals such as calcium, and bases like sodium carbonate. Aqueous acids have a pH of less than 7, where an acid of lower pH is typically stronger, and turn blue litmus paper red...
ic residues asparagine and glycine form a "claw" of sorts which easily stabilizes divalent cations. Calcium
Calcium
Calcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...
ions make for the best-fitting cations stabilizing the surfactin conformation and functioning as an assembly template for the formation of micelles. When surfactin penetrates the outer sheet, its fatty acid chain interacts with the acyl
Acyl
An acyl group is a functional group derived by the removal of one or more hydroxyl groups from an oxoacid, including inorganic acids.In organic chemistry, the acyl group is usually derived from a carboxylic acid . Therefore, it has the formula RCO-, where R represents an alkyl group that is...
chains of the phospholipid
Phospholipid
Phospholipids are a class of lipids that are a major component of all cell membranes as they can form lipid bilayers. Most phospholipids contain a diglyceride, a phosphate group, and a simple organic molecule such as choline; one exception to this rule is sphingomyelin, which is derived from...
s, with its headgroup in proximity to the phospholipids polar heads. Attachment of a cation to causes the complex to cross the bilipidic layer undergoing a flip-flop
Flip-flop
Flip-flops, thongs, Japanese sandals, or jandals are an open type of outdoor footwear, consisting of a flat sole held loosely on the foot by a Y-shaped strap, like a thin thong, that passes between the first and second toes and around either side of the foot...
. The headgroup aligns itself with the phospholipids of the inner sheet and the fatty acid chain interacts with the phospholipids acyl chains. The cation is then delivered into the intracellular medium.
Pore-forming effect
The pore-forming (ion channelIon channel
Ion channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of cells by allowing the flow of ions down their electrochemical gradient. They are present in the membranes that surround all biological cells...
) effect is characterized by the formation of cationic channels. It would require surfactin to self-associate inside the membrane, since it cannot span across the cellular membrane. Supramolecular-like structures by successive self-association
Molecular self-assembly
Molecular self-assembly is the process by which molecules adopt a defined arrangement without guidance or management from an outside source. There are two types of self-assembly, intramolecular self-assembly and intermolecular self-assembly...
could then form a channel. This hypothesis for the most part applies only to uncharged membranes where there is a minimal energy barrier between outer and inner membrane leaflets.
Detergent effect
The detergent effect draws on surfactin's ability to insert its fatty acid chain into the bilipidic layer causing disorganization leading to membrane permeability. Insertion of several surfactin molecules into the membrane can lead to the formation of mixed micelles by self-association and bilayer influenced by fatty chain hydrophobicity ultimately leading to bilayer solubilization.Biological properties
Surfactin has a nonspecific mode of action, which originates both benefits and disadvantages. It’s advantageous in the sense that surfactin can act on many kinds of cell membranes, both Gram-positive and Gram-negative. Its non-specificity also has bearing on its tendency to not produce resistant strains of bacteriaAntibiotic resistance
Antibiotic resistance is a type of drug resistance where a microorganism is able to survive exposure to an antibiotic. While a spontaneous or induced genetic mutation in bacteria may confer resistance to antimicrobial drugs, genes that confer resistance can be transferred between bacteria in a...
. Consequently, this efficient mode of cell destruction is indiscriminate, and attacks red blood cells with deadly efficiency.
Antibacterial and antiviral properties
Surfactin, true to its antibiotic nature, has a very significant antibacterial property, as it is capable of penetrating the cell membranes of all types of bacteria. There are two main types of bacteria and they are Gram-negativeGram-negative
Gram-negative bacteria are bacteria that do not retain crystal violet dye in the Gram staining protocol. In a Gram stain test, a counterstain is added after the crystal violet, coloring all Gram-negative bacteria with a red or pink color...
and Gram-positive. The two bacteria types differ in the composition of their membrane. The Gram-negative bacteria have an outer lipopolysaccharide
Lipopolysaccharide
Lipopolysaccharides , also known as lipoglycans, are large molecules consisting of a lipid and a polysaccharide joined by a covalent bond; they are found in the outer membrane of Gram-negative bacteria, act as endotoxins and elicit strong immune responses in animals.-Functions:LPS is the major...
membrane and a thin peptidoglycan layer followed by a phospholipids bilayer, whereas the Gram-positive bacteria lack the outer membrane and carry a thicker peptidoglycan
Peptidoglycan
Peptidoglycan, also known as murein, is a polymer consisting of sugars and amino acids that forms a mesh-like layer outside the plasma membrane of bacteria , forming the cell wall. The sugar component consists of alternating residues of β- linked N-acetylglucosamine and N-acetylmuramic acid...
layer as well as a phospholipids bilayer. This is an essential factor that contributes to surfactin’s detergent-like activity as it is able to create a permeable environment for the lipid bilayer and causes disruption that solubilizes the membrane.
For surfactin to carry out its antibacterial property successfully, the bacterium needs to be treated with a high concentration. In fact, surfactin needs to be in concentrations between 12–50 µg
Gram
The gram is a metric system unit of mass....
/ml
Litér
- External links :*...
in order for it to carry out minimal antibacterial effects. This is also known as the minimum inhibitory concentration (MIC).
The antiviral effects of surfactin distinguish this antibiotic from others. This property is such because surfactin has been found to disintegrate enveloped virus
Virus
A virus is a small infectious agent that can replicate only inside the living cells of organisms. Viruses infect all types of organisms, from animals and plants to bacteria and archaea...
es. Surfactin not only disintegrates the viral lipid enveloped, but also the capsid
Capsid
A capsid is the protein shell of a virus. It consists of several oligomeric structural subunits made of protein called protomers. The observable 3-dimensional morphological subunits, which may or may not correspond to individual proteins, are called capsomeres. The capsid encloses the genetic...
of the virus through ion channel formations. This process has been proven through test on several envelop viruses such as HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
and HSV
Herpes simplex virus
Herpes simplex virus 1 and 2 , also known as Human herpes virus 1 and 2 , are two members of the herpes virus family, Herpesviridae, that infect humans. Both HSV-1 and HSV-2 are ubiquitous and contagious...
. Also, the isoforms of the fatty acid chain containing 14 or 15 carbon atoms exhibited an improvement in inactivation of the viral envelops. Unfortunately, surfactin only affected cell-free viruses and those that had penetrated the cell were unaffected. Concurrently, if surfactin were exposed to a high medium of protein or lipid concentrations, its antiviral activity would be limited. This is also known as the buffer effect and is a significant drawback in surfactin’s antiviral activity.
Toxicity
Surfactin has only one drawback: its non specific cytotoxicity. This is seen as surfactin has the ability to lyseLysis
Lysis refers to the breaking down of a cell, often by viral, enzymic, or osmotic mechanisms that compromise its integrity. A fluid containing the contents of lysed cells is called a "lysate"....
a cell. The hemolytic effect has been the result of surfactin having the ability to lyse red blood cells that is enough to warrant caution if used intravascularly. Fortunately, these results were seen at high concentrations of about 40 µM to 60 µM. These concentrations also exhibited the effect of proliferating cells in vitro though it also was the for this type of cells. At concentrations below 25 µM, toxicity effects of surfactin are not significant.