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Streptomycin is an
antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy, ...
medication used to treat a number of bacterial infections, including
tuberculosis Tuberculosis (TB) is an infectious disease usually caused by ''Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, in ...
, ''Mycobacterium avium'' complex,
endocarditis Endocarditis is an inflammation of the inner layer of the heart, the endocardium. It usually involves the heart valves. Other structures that may be involved include the interventricular septum, the chordae tendineae, the mural endocardium, or the ...
,
brucellosis Brucellosis is a highly contagious zoonosis caused by ingestion of Pasteurization, unpasteurized milk or undercooked meat from infected animals, or close contact with their secretions. It is also known as undulant fever, Malta fever, and Mediterra ...
, ''Burkholderia'' infection, plague,
tularemia Tularemia, also known as rabbit fever, is an infectious disease caused by the bacterium ''Francisella tularensis''. Symptoms may include fever, skin ulcers, and lymphadenopathy, enlarged lymph nodes. Occasionally, a form that results in pneumonia ...
, and rat bite fever. For active tuberculosis it is often given together with
isoniazid Isoniazid, also known as isonicotinic acid hydrazide (INH), is an antibiotic used for the Tuberculosis management, treatment of tuberculosis. For active tuberculosis it is often used together with rifampicin, pyrazinamide, and either streptomyci ...
,
rifampicin Rifampicin, also known as rifampin, is an ansamycin antibiotic used to treat several types of bacterial infections, including tuberculosis (TB), mycobacterium avium complex, ''Mycobacterium avium'' complex, leprosy, and Legionnaires’ disease. ...
, and
pyrazinamide Pyrazinamide is a medication used to treat tuberculosis Tuberculosis (TB) is an infectious disease usually caused by ''Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect o ...
. It is administered by injection into a vein or
muscle Skeletal muscles (commonly referred to as muscles) are Organ (biology), organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other ...
. Common side effects include
vertigo Vertigo is a condition where a person has the sensation of movement or of surrounding objects moving when they are not. Often it feels like a spinning or swaying movement. This may be associated with nausea, vomiting, sweating, or difficulties w ...
, vomiting, numbness of the face, fever, and rash. Use during
pregnancy Pregnancy is the time during which one or more offspring develops (gestation, gestates) inside a woman, woman's uterus (womb). A multiple birth, multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occur ...
may result in permanent
deafness Deafness has varying definitions in cultural and medical contexts. In medical contexts, the meaning of deafness is hearing loss that precludes a person from understanding spoken language, an Audiology, audiological condition. In this context it ...
in the developing baby. Use appears to be safe while
breastfeeding Breastfeeding, or nursing, is the process by which human breast milk is fed to a child. Breast milk may be from the breast, or may be expressed by hand or pumped and fed to the infant. The World Health Organization (WHO) recommends that br ...
. It is not recommended in people with
myasthenia gravis Myasthenia gravis (MG) is a long-term neuromuscular junction disease that leads to varying degrees of skeletal muscle weakness. The most commonly affected muscles are those of the eyes, face, and swallowing. It can result in double vision ...
or other
neuromuscular disorders A neuromuscular disease is any disease affecting the peripheral nervous system (PNS), the neuromuscular junction, or skeletal muscle, all of which are components of the motor unit. Damage to any of these structures can cause muscle atrophy and weak ...
. Streptomycin is an
aminoglycoside Aminoglycoside is a medicinal chemistry, medicinal and bacteriology, bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside ...
. It works by blocking the ability of
30S ribosomal subunits The prokaryotic small ribosomal subunit, or 30Svedberg, S subunit, is the smaller subunit of the 70S ribosome found in prokaryotes. It is a complex of the 16S ribosomal RNA (rRNA) and 19 proteins. This complex is implicated in the binding of tr ...
to make proteins, which results in bacterial death. Albert Schatz first isolated streptomycin in 1943 from ''
Streptomyces griseus ''Streptomyces griseus'' is a species of bacteria in the genus ''Streptomyces'' commonly found in soil. A few strain (biology), strains have been also reported from deep-sea sediments. It is a Gram-positive bacterium with high GC content. Along ...
''. It is on the
World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health s ...
. The World Health Organization classifies it as critically important for human medicine.


Uses


Medication

*
Infective endocarditis Infective endocarditis is an infection of the endocardium, inner surface of the heart, usually the heart valve, valves. Signs and symptoms may include fever, petechia, small areas of bleeding into the skin, heart murmur, feeling tired, and anemia, ...
: An infection of the endocardium caused by
enterococcus ''Enterococcus'' is a large genus of lactic acid bacteria of the Phylum (biology), phylum Bacillota. Enterococci are gram-positive cocci that often occur in pairs (diplococcus, diplococci) or short chains, and are difficult to distinguish from S ...
; used when the organism is not sensitive to
gentamicin Gentamicin is an antibiotic used to treat several types of bacterial infections. This may include osteomyelitis, bone infections, endocarditis, pelvic inflammatory disease, meningitis, pneumonia, urinary tract infections, and sepsis among other ...
*
Tuberculosis Tuberculosis (TB) is an infectious disease usually caused by ''Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, in ...
: Used in combination with other antibiotics. For active tuberculosis it is often given together with
isoniazid Isoniazid, also known as isonicotinic acid hydrazide (INH), is an antibiotic used for the Tuberculosis management, treatment of tuberculosis. For active tuberculosis it is often used together with rifampicin, pyrazinamide, and either streptomyci ...
,
rifampicin Rifampicin, also known as rifampin, is an ansamycin antibiotic used to treat several types of bacterial infections, including tuberculosis (TB), mycobacterium avium complex, ''Mycobacterium avium'' complex, leprosy, and Legionnaires’ disease. ...
, and
pyrazinamide Pyrazinamide is a medication used to treat tuberculosis Tuberculosis (TB) is an infectious disease usually caused by ''Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect o ...
. It is not the first-line treatment, except in medically under-served populations where the cost of more expensive treatments is prohibitive. It may be useful in cases where resistance to other drugs is identified. * Plague (''
Yersinia pestis ''Yersinia pestis'' (''Y. pestis''; formerly ''Pasteurella pestis'') is a gram-negative bacteria, gram-negative, non-motile bacteria, non-motile, coccobacillus Bacteria, bacterium without spores that is related to both ''Yersinia pseudotuberculos ...
''): Has historically been used as the first-line treatment. However streptomycin is approved for this purpose only by the US
Food and Drug Administration The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
. * In
veterinary medicine Veterinary medicine is the branch of medicine Medicine is the science and Praxis (process), practice of caring for a patient, managing the diagnosis, prognosis, Preventive medicine, prevention, therapy, treatment, Palliative care, palliatio ...
, streptomycin is the first-line antibiotic for use against
gram negative The gram (originally gramme; SI unit symbol g) is a unit of mass in the International System of Units (SI) equal to one one thousandth of a kilogram. Originally defined as of 1795 as "the absolute weight of a volume Volume is a measu ...
bacteria in large animals (
horse The horse (''Equus ferus caballus'') is a Domestication, domesticated, odd-toed ungulate, one-toed, ungulate, hoofed mammal. It belongs to the taxonomic family Equidae and is one of two Extant taxon, extant subspecies of wild horse, ''Equus fer ...
s,
cattle Cattle (''Bos taurus'') are large, domestication, domesticated, Cloven hoof, cloven-hooved, herbivores. They are a prominent modern member of the subfamily Bovinae and the most widespread species of the genus ''Bos''. Adult females are referr ...
,
sheep Sheep or domestic sheep (''Ovis aries'') are domesticated, ruminant mammals typically kept as livestock. Although the term ''sheep'' can apply to other species in the genus ''Ovis'', in everyday usage it almost always refers to domesticated sh ...
, etc.). It is commonly combined with procaine
penicillin Penicillins (P, PCN or PEN) are a group of beta-lactam antibiotic, β-lactam antibiotics originally obtained from ''Penicillium'' Mold (fungus), moulds, principally ''Penicillium chrysogenum, P. chrysogenum'' and ''Penicillium rubens, P. ru ...
for intramuscular injection. *
Tularemia Tularemia, also known as rabbit fever, is an infectious disease caused by the bacterium ''Francisella tularensis''. Symptoms may include fever, skin ulcers, and lymphadenopathy, enlarged lymph nodes. Occasionally, a form that results in pneumonia ...
infections have been treated mostly with streptomycin. Streptomycin is traditionally given intramuscularly, and in many nations is only licensed to be administered intramuscularly, though in some regions the drug may also be administered
intravenous Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...
ly.


Pesticide

Streptomycin also is used as a pesticide, to combat the growth of bacteria beyond human applications. Streptomycin controls bacterial diseases of certain fruit, vegetables, seed, and ornamental crops. A major use is in the control of fireblight on apple and pear trees. As in medical applications, extensive use can be associated with the development of resistant strains. Streptomycin could potentially be used to control
cyanobacteria Cyanobacteria (), also known as Cyanophyta, are a phylum (biology), phylum of gram-negative bacteria that obtain energy via photosynthesis. The name ''cyanobacteria'' refers to their color (), which similarly forms the basis of cyanobacteria's ...
l blooms in ornamental ponds and aquaria. While some antibacterial antibiotics are inhibitory to certain eukaryotes, this seems not to be the case for streptomycin, especially in the case of anti-fungal activity.


Cell culture

Streptomycin, in combination with penicillin, is used in a standard antibiotic cocktail to prevent bacterial infection in cell culture.


Protein purification

When purifying protein from a biological extract, streptomycin sulfate is sometimes added as a means of removing nucleic acids. Since it binds to ribosomes and precipitates out of solution, it serves as a method for removing rRNA, mRNA, and even DNA if the extract is from a prokaryote.


Side effects

The most concerning side effects, as with other aminoglycosides, are kidney toxicity and ear toxicity. Transient or permanent deafness may result. The vestibular portion of cranial nerve VIII (the
vestibulocochlear nerve The vestibulocochlear nerve or auditory vestibular nerve, also known as the eighth cranial nerve, cranial nerve VIII, or simply CN VIII, is a cranial nerve Cranial nerves are the nerves that emerge directly from the brain (including the b ...
) can be affected, resulting in
tinnitus Tinnitus is the perception of sound when no corresponding external sound is present. Nearly everyone experiences a faint "normal tinnitus" in a completely quiet room; but it is of concern only if it is bothersome, interferes with normal hearin ...
,
vertigo Vertigo is a condition where a person has the sensation of movement or of surrounding objects moving when they are not. Often it feels like a spinning or swaying movement. This may be associated with nausea, vomiting, sweating, or difficulties w ...
,
ataxia Ataxia is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in eye movements. Ataxia is a clinical manifestation indicating dysfunction of ...
, kidney toxicity, and can potentially interfere with diagnosis of kidney malfunction. Common side effects include
vertigo Vertigo is a condition where a person has the sensation of movement or of surrounding objects moving when they are not. Often it feels like a spinning or swaying movement. This may be associated with nausea, vomiting, sweating, or difficulties w ...
, vomiting, numbness of the face, fever, and rash. Fever and rashes may result from persistent use. Use is not recommended during pregnancy. Congenital deafness has been reported in children whose mothers received streptomycin during pregnancy. Use appears to be okay while
breastfeeding Breastfeeding, or nursing, is the process by which human breast milk is fed to a child. Breast milk may be from the breast, or may be expressed by hand or pumped and fed to the infant. The World Health Organization (WHO) recommends that br ...
. It is not recommended in people with
myasthenia gravis Myasthenia gravis (MG) is a long-term neuromuscular junction disease that leads to varying degrees of skeletal muscle weakness. The most commonly affected muscles are those of the eyes, face, and swallowing. It can result in double vision ...
.


Mechanism of action

Streptomycin functions as a
protein synthesis inhibitor A protein synthesis inhibitor is a compound that stops or slows the growth or proliferation of cells by disrupting the processes that lead directly to the generation of new proteins. While a broad interpretation of this definition could be used t ...
. It binds to the small 16S rRNA of the 30S ribosomal subunit irreversibly, interfering with the binding of formyl-methionyl-tRNA to the 30S subunit. This causes codon misreading, inhibition of protein synthesis, and ultimately death of the cell through mechanisms that are not well understood. Speculation indicates that the binding of the molecule to the 30S subunit interferes with 30S subunit association with the
mRNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein. mRNA is ...
strand. This results in an unstable ribosomal-mRNA complex, leading to premature stopping of protein synthesis, leading to cell death. As human and bacteria both have ribosomes, streptomycin has significant side effects in humans. At low concentrations, however, streptomycin inhibits only bacterial growth. Streptomycin is an antibiotic that inhibits both Gram-positive and Gram-negative bacteria, and is therefore a useful broad-spectrum antibiotic.


History

Streptomycin was first isolated on October 19, 1943, by Albert Schatz, a PhD student in the laboratory of Selman Abraham Waksman at
Rutgers University Rutgers University (; RU), officially Rutgers, The State University of New Jersey, is a Public university, public land-grant research university consisting of four campuses in New Jersey. Chartered in 1766, Rutgers was originally called Queen's ...
in a research project funded by Merck and Co. Waksman and his laboratory staff discovered several antibiotics, including actinomycin, clavacin, streptothricin, streptomycin, grisein,
neomycin Neomycin is an aminoglycoside Aminoglycoside is a medicinal chemistry, medicinal and bacteriology, bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the mo ...
, fradicin, candicidin, and candidin. Of these, streptomycin and neomycin found extensive application in the treatment of numerous infectious diseases. Streptomycin was the first
antibiotic An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting pathogenic bacteria, bacterial infections, and antibiotic medications are widely used in the therapy, ...
cure for
tuberculosis Tuberculosis (TB) is an infectious disease usually caused by ''Mycobacterium tuberculosis'' (MTB) bacteria. Tuberculosis generally affects the lungs, but it can also affect other parts of the body. Most infections show no symptoms, in ...
(TB). In 1952 Waksman was the recipient of the
Nobel Prize in Physiology or Medicine The Nobel Prize in Physiology or Medicine is awarded yearly by the Nobel Assembly at the Karolinska Institute, Nobel Assembly at the Karolinska Institutet, Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Pr ...
in recognition "for his discovery of streptomycin, the first antibiotic active against tuberculosis". Waksman was later accused of playing down the role of Schatz who did the work under his supervision, claiming that Elizabeth Bugie had a more important role in its development. Schatz sued both Dr. Waksman and the Rutgers Research and Endowment Foundation, wanting to be given credited as co-discover and receive the royalties for the streptomycin. By the end of the settlement, Waksman would receive a 10% royalty, while Schatz got 3% and compensation for his missed royalties. The rest of the lab shared the remaining 7% of the royalties, in which Bugie received 0.2%. Bugie was pursuing a master's degree in Waksman's lab at Rutgers University at this time. Prior to this, she received her bachelor's degree in microbiology at New Jersey College for Women. Although Bugie was considered to be the second author on the ''Proceedings of the Society for Experimental Biology'' paper, she was not listed on the patent submission. Bugie's contributions to Wakeman's lab were great. In addition to her work on streptomycin, she also helped develop other antimicrobial substances, had two peer-reviewed publications, and researched the use of antimicrobals against plant pathogens, among several other important contributions to the scientific field, particularly in regard to microbiology. The Rutgers team reported streptomycin in the medical literature in January 1944. Within months they began working with William Feldman and H. Corwin Hinshaw of the
Mayo Clinic The Mayo Clinic () is a Nonprofit organization, nonprofit American Academic health science centre, academic Medical centers in the United States, medical center focused on integrated health care, Mayo Clinic College of Medicine and Science, e ...
with hopes of starting a human clinical trial of streptomycin in tuberculosis. The difficulty at first was even producing enough streptomycin to do a trial, because the research laboratory methods of creating small batches had not yet been
translated Translation is the communication of the Meaning (linguistic), meaning of a #Source and target languages, source-language text by means of an Dynamic and formal equivalence, equivalent #Source and target languages, target-language text. The ...
to commercial large-batch production. They managed to do an animal study in a few guinea pigs with just 10 grams of the scarce drug, demonstrating survival. This was just enough evidence to get Merck & Co. to divert some resources from the young penicillin production program to start work toward streptomycin production. At the end of World War II, the United States Army experimented with streptomycin to treat life-threatening infections at a military hospital in
Battle Creek, Michigan Battle Creek is a city in the U.S. state of Michigan, in northwest Calhoun County, Michigan, Calhoun County, at the confluence of the Kalamazoo River, Kalamazoo and Battle Creek River, Battle Creek rivers. It is the principal city of the Battle C ...
. The first person who was treated with streptomycin did not survive; the second person survived but became blind as a side effect of the treatment. In March 1946, the third person— Robert J. Dole, later Majority Leader of the United States Senate and presidential nominee—experienced a rapid and robust recovery. The first randomized trial of streptomycin against pulmonary tuberculosis was carried out in 1946 through 1948 by the MRC Tuberculosis Research Unit under the chairmanship of Geoffrey Marshall (1887–1982). The trial was neither
double-blind In a blind or blinded experiment, information which may influence the participants of the experiment An experiment is a procedure carried out to support or refute a hypothesis, or determine the efficacy or likelihood of something previousl ...
nor placebo-controlled. It is widely accepted to have been the first randomized curative trial. Results showed efficacy against TB, albeit with minor toxicity and acquired bacterial resistance to the drug.


New Jersey

Because streptomycin was isolated from a microbe discovered on New Jersey soil, and because of its activity against tuberculosis and Gram negative organisms, and in recognition of both the microbe and the antibiotic in the history of New Jersey, ''S. griseus'' was nominated as the Official New Jersey state microbe. The draft legislation was submitted by Senator Sam Thompson (R-12) in May 2017 as bill S3190 and Assemblywoman Annette Quijano (D-20) in June 2017 as bill A31900. The bill was passed on 2018-01-08 The bill designates Streptomyces griseus as New Jersey State Microbe (New Jersey Senate Bill 3190 (2017). Passed in January 2018.


See also

* Philip D'Arcy Hart – The British medical researcher and pioneer in tuberculosis treatment in the early twentieth century.


References


Further reading

* * . The history behind the discovery of streptomycin. * *


External links

* {{Authority control Aminoglycoside antibiotics Anti-tuberculosis drugs Guanidines Secondary amines World Health Organization essential medicines Wikipedia medicine articles ready to translate