Gramicidin S
Encyclopedia
Gramicidin S or Gramicidin Soviet is an antibiotic effective against some Gram positive and Gram negative bacteria as well as some fungi. It is a derivative of gramicidin
, produced by the Gram positive bacterium Bacillus brevis. Gramicidin S is a cyclodecapeptide, constructed as two identical pentapeptides joined head to tail, formally written as cyclo(-Val
-Orn
-Leu
-D-Phe
-Pro
-)2. That is to say, it forms a ring structure composed of five different amino acids, each one used twice within the structure. Another interesting point is that it utilizes two amino acids uncommon in peptides: ornithine
as well as the atypical stereoisomer of phenylalanine
. It is synthesized by gramicidin S synthetase.
to Great Britain
via the International Red Cross in a collaborative effort to establish the exact structure. English chemist Richard Synge proved that the compound was an original antibiotic and a polypeptide using paper chromatography. He would later go on to receive the Nobel Prize
for his work in chromatography. The crystal structure was finally established by Dorothy Hodgkin and Gerchardt Schmidt. The importance of Gramicidin S and antibiotic research in general was so great that Gause was not persecuted during the period of Lysenkoism
in the USSR, while many of his colleagues were being executed. Indeed, it was his need for developing new strains to mass produce antibiotics that allowed politically sanctioned collaborations with geneticist
s like Joseph Rapoport and Alexander Malinovsky, who would both actively participate in the downfall of Lysenkoism.
, which is a linear peptide
and forms a beta helix in cellular membrane
s. The mode of action is not entirely agreed upon, but it is generally accepted that it is the disruption of the barrier properties of cellular membranes which causes cell death. Recent research reveals that Gramicidin S interacts more so with anionic
membranes (such as those of bacteria) vs. zwitterion
ic membranes and more fluid membranes. It has a molecular mass
of ca. 1,140 and is a solid, usually encapsulated in two-percent sterile spirit solution. In vitro
assays show it has a MIC
of 5-15 μg/mL.
fungi. Like Gramicidin D, Gramicidin S causes hemolysis
at low concentrations, thus is not an effective drug for the treatment of systemic infections. Additionally, Gramicidin S has been employed as a spermicide and therapeutic for genital ulcers caused by sexually transmitted disease
.
Gramicidin
Gramicidin is a heterogeneous mixture of six antibiotic compounds, gramicidins A, B and C, making up 80%, 6%,and 14% respectively, all of which are obtained from the soil bacterial species Bacillus brevis and called collectively gramicidin D. Gramicidin D are linear pentadecapeptides; that is...
, produced by the Gram positive bacterium Bacillus brevis. Gramicidin S is a cyclodecapeptide, constructed as two identical pentapeptides joined head to tail, formally written as cyclo(-Val
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...
-Orn
Ornithine
Ornithine is an amino acid that plays a role in the urea cycle.-Role in urea cycle:L-Ornithine is one of the products of the action of the enzyme arginase on L-arginine, creating urea. Therefore, ornithine is a central part of the urea cycle, which allows for the disposal of excess nitrogen....
-Leu
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...
-D-Phe
Phenylalanine
Phenylalanine is an α-amino acid with the formula C6H5CH2CHCOOH. This essential amino acid is classified as nonpolar because of the hydrophobic nature of the benzyl side chain. L-Phenylalanine is an electrically neutral amino acid, one of the twenty common amino acids used to biochemically form...
-Pro
Proline
Proline is an α-amino acid, one of the twenty DNA-encoded amino acids. Its codons are CCU, CCC, CCA, and CCG. It is not an essential amino acid, which means that the human body can synthesize it. It is unique among the 20 protein-forming amino acids in that the α-amino group is secondary...
-)2. That is to say, it forms a ring structure composed of five different amino acids, each one used twice within the structure. Another interesting point is that it utilizes two amino acids uncommon in peptides: ornithine
Ornithine
Ornithine is an amino acid that plays a role in the urea cycle.-Role in urea cycle:L-Ornithine is one of the products of the action of the enzyme arginase on L-arginine, creating urea. Therefore, ornithine is a central part of the urea cycle, which allows for the disposal of excess nitrogen....
as well as the atypical stereoisomer of phenylalanine
Phenylalanine
Phenylalanine is an α-amino acid with the formula C6H5CH2CHCOOH. This essential amino acid is classified as nonpolar because of the hydrophobic nature of the benzyl side chain. L-Phenylalanine is an electrically neutral amino acid, one of the twenty common amino acids used to biochemically form...
. It is synthesized by gramicidin S synthetase.
History
Gramicidin S was discovered by Russian microbiologist Georgyi Frantsevitch Gause and his wife Maria Brazhnikova in 1942. Within the year Gramicidin S was being used in Soviet military hospitals to treat infection and eventually found usage at the front lines of combat by 1946. Gause was awarded the Stalin Prize for Medicine for his discovery in 1946. In 1944, Gramicidin S was sent by the Ministry of Health of the USSRMinistry of Health (Soviet Union)
The Ministry of Health of the Union of Soviet Socialist Republics , formed on 15 March 1946, was one of the most important government offices in the Soviet Union. It was formerly known as the People's Commissariat for Health...
to Great Britain
Great Britain
Great Britain or Britain is an island situated to the northwest of Continental Europe. It is the ninth largest island in the world, and the largest European island, as well as the largest of the British Isles...
via the International Red Cross in a collaborative effort to establish the exact structure. English chemist Richard Synge proved that the compound was an original antibiotic and a polypeptide using paper chromatography. He would later go on to receive the Nobel Prize
Nobel Prize
The Nobel Prizes are annual international awards bestowed by Scandinavian committees in recognition of cultural and scientific advances. The will of the Swedish chemist Alfred Nobel, the inventor of dynamite, established the prizes in 1895...
for his work in chromatography. The crystal structure was finally established by Dorothy Hodgkin and Gerchardt Schmidt. The importance of Gramicidin S and antibiotic research in general was so great that Gause was not persecuted during the period of Lysenkoism
Lysenkoism
Lysenkoism, or Lysenko-Michurinism, also denotes the biological inheritance principle which Trofim Lysenko subscribed to and which derive from theories of the heritability of acquired characteristics, a body of biological inheritance theory which departs from Mendelism and that Lysenko named...
in the USSR, while many of his colleagues were being executed. Indeed, it was his need for developing new strains to mass produce antibiotics that allowed politically sanctioned collaborations with geneticist
Geneticist
A geneticist is a biologist who studies genetics, the science of genes, heredity, and variation of organisms. A geneticist can be employed as a researcher or lecturer. Some geneticists perform experiments and analyze data to interpret the inheritance of skills. A geneticist is also a Consultant or...
s like Joseph Rapoport and Alexander Malinovsky, who would both actively participate in the downfall of Lysenkoism.
Structure and Pharmacological effect
Structurally, Gramicidin S differs from Gramicidin DGramicidin
Gramicidin is a heterogeneous mixture of six antibiotic compounds, gramicidins A, B and C, making up 80%, 6%,and 14% respectively, all of which are obtained from the soil bacterial species Bacillus brevis and called collectively gramicidin D. Gramicidin D are linear pentadecapeptides; that is...
, which is a linear peptide
Peptide
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...
and forms a beta helix in cellular membrane
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...
s. The mode of action is not entirely agreed upon, but it is generally accepted that it is the disruption of the barrier properties of cellular membranes which causes cell death. Recent research reveals that Gramicidin S interacts more so with anionic
Ion
An ion is an atom or molecule in which the total number of electrons is not equal to the total number of protons, giving it a net positive or negative electrical charge. The name was given by physicist Michael Faraday for the substances that allow a current to pass between electrodes in a...
membranes (such as those of bacteria) vs. zwitterion
Zwitterion
In chemistry, a zwitterion is a neutral molecule with a positive and a negative electrical charge at different locations within that molecule. Zwitterions are sometimes also called inner salts.-Examples:...
ic membranes and more fluid membranes. It has a molecular mass
Molecular mass
The molecular mass of a substance is the mass of one molecule of that substance, in unified atomic mass unit u...
of ca. 1,140 and is a solid, usually encapsulated in two-percent sterile spirit solution. In vitro
In vitro
In vitro refers to studies in experimental biology that are conducted using components of an organism that have been isolated from their usual biological context in order to permit a more detailed or more convenient analysis than can be done with whole organisms. Colloquially, these experiments...
assays show it has a MIC
Minimum inhibitory concentration
In microbiology, minimum inhibitory concentration is the lowest concentration of an antimicrobial that will inhibit the visible growth of a microorganism after overnight incubation. Minimum inhibitory concentrations are important in diagnostic laboratories to confirm resistance of microorganisms...
of 5-15 μg/mL.
Use
Gramicidin S has historically been employed as a topical antibiotic for the treatment of infections from superficial wounds. It exhibits strong antibiotic activity against a broad spectrum of Gram negative and Gram-positive bacteria and against several pathogenicfungi. Like Gramicidin D, Gramicidin S causes hemolysis
Hemolysis
Hemolysis —from the Greek meaning "blood" and meaning a "loosing", "setting free" or "releasing"—is the rupturing of erythrocytes and the release of their contents into surrounding fluid...
at low concentrations, thus is not an effective drug for the treatment of systemic infections. Additionally, Gramicidin S has been employed as a spermicide and therapeutic for genital ulcers caused by sexually transmitted disease
Sexually transmitted disease
Sexually transmitted disease , also known as a sexually transmitted infection or venereal disease , is an illness that has a significant probability of transmission between humans by means of human sexual behavior, including vaginal intercourse, oral sex, and anal sex...
.