Streptomycin
Encyclopedia
Streptomycin is 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...

 drug, the first of a class of drugs called aminoglycoside
Aminoglycoside
An aminoglycoside is a molecule or a portion of a molecule composed of amino-modifiedsugars.Several aminoglycosides function as antibiotics that are effective against certain types of bacteria...

s to be discovered, and was the first antibiotic remedy for tuberculosis
Tuberculosis
Tuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body...

. It is derived from the actinobacterium
Actinobacteria
Actinobacteria are a group of Gram-positive bacteria with high guanine and cytosine content. They can be terrestrial or aquatic. Actinobacteria is one of the dominant phyla of the bacteria....

 Streptomyces griseus
Streptomyces griseus
Streptomyces griseus is a member bacterial species of the genus Streptomyces and are commonly found in soil. A few strains have been also reported from deep sea sediments. These are Gram positive bacterium with high GC content. Along with most other streptomycetes S...

. Streptomycin is a bactericidal antibiotic. Streptomycin cannot be given orally, but must be administered by regular intramuscular injection
Intramuscular injection
Intramuscular injection is the injection of a substance directly into a muscle. In medicine, it is one of several alternative methods for the administration of medications . It is used for particular forms of medication that are administered in small amounts...

s. An adverse effect of this medicine is ototoxicity
Ototoxicity
Ototoxicity is damage to the ear , specifically the cochlea or auditory nerve and sometimes the vestibular system, by a toxin. It is commonly medication-induced; ototoxic drugs include antibiotics such as the aminoglycoside gentamicin, loop diuretics such as furosemide, and platinum-based...

.

Mechanism of action

Streptomycin is a protein synthesis inhibitor
Protein synthesis inhibitor
A protein synthesis inhibitor is a substance that stops or slows the growth or proliferation of cells by disrupting the processes that lead directly to the generation of new proteins....

. It binds to the small 16S rRNA of the 30S subunit of the bacterial ribosome, interfering with the binding of formyl-methionyl-tRNA to the 30S subunit. This leads to codon misreading, eventual inhibition of protein synthesis and ultimately death of microbial cells through mechanisms that are still not understood. Humans have structurally different ribosomes from bacteria, thereby allowing the selectivity of this antibiotic for bacteria. However at low concentrations Streptomycin only inhibits growth of the bacteria by inducing prokaryotic ribosomes to misread mRNA. 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
Albert Schatz (scientist)
Albert Schatz was the co-discoverer of streptomycin, the first antibiotic remedy used to treat tuberculosis and a number of other diseases...

, a graduate student, in the laboratory of Selman Abraham Waksman at Rutgers University
Rutgers University
Rutgers, The State University of New Jersey , is the largest institution for higher education in New Jersey, United States. It was originally chartered as Queen's College in 1766. It is the eighth-oldest college in the United States and one of the nine Colonial colleges founded before the American...

. Dr. Waksman and his laboratory discovered several antibiotics, including actinomycin
Actinomycin
The actinomycins are a class of polypeptide antibiotics isolated from soil bacteria of the genus Streptomyces, of which the most significant is actinomycin D. It was the first antibiotic isolated by Selman Waksman and his co-worker H. B. Woodruff in 1940.-Mechanism:Actinomycin D is primarily used...

, clavacin, streptothricin, streptomycin, grisein, neomycin
Neomycin
Neomycin is an aminoglycoside antibiotic that is found in many topical medications such as creams, ointments, and eyedrops. The discovery of Neomycin dates back to 1949. It was discovered in the lab of Selman Waksman, who was later awarded the Nobel Prize in Physiology and medicine in 1951...

, fradicin, candicidin
Candicidin
Candicidin is an antibiotic....

 and candidin. Of these, streptomycin and neomycin found extensive application in the treatment of numerous infectious diseases. Streptomycin was the first 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...

 that could be used to cure the disease tuberculosis
Tuberculosis
Tuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body...

; early production of the drug was dominated by Merck & Co.
Merck & Co.
Merck & Co., Inc. , also known as Merck Sharp & Dohme or MSD outside the United States and Canada, is one of the largest pharmaceutical companies in the world. The Merck headquarters is located in Whitehouse Station, New Jersey, an unincorporated area in Readington Township...

 under George W. Merck
George W. Merck
George Wilhelm Herman Emanuel Merck , was the president of Merck & Co. from 1925 to 1950.-Biography:Born in New York and raised in Llewellyn Park, New Jersey, he attended Harvard College, graduating in 1915. World War I prevented him from pursuing an advanced degree in Germany; instead, he joined...

.

The first randomized trial of streptomycin against pulmonary tuberculosis was carried out in 1946-1947 by the MRC Tuberculosis Research Unit under the chairmanship of Sir Geoffrey Marshall (1887–1982). The trial was both double-blind and placebo-controlled
Placebo
A placebo is a simulated or otherwise medically ineffectual treatment for a disease or other medical condition intended to deceive the recipient...

. It is widely accepted to have been the first randomised curative trial. Results showed efficacy against TB, albeit with minor toxicity and acquired bacterial resistance
Antibiotic 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...

 to the drug.

Treatment of diseases

  • Infective endocarditis
    Infective endocarditis
    Infective endocarditis is a form of endocarditis, or inflammation, of the inner tissue of the heart, such as its valves, caused by infectious agents. The agents are usually bacterial, but other organisms can also be responsible....

     caused by enterococcus when the organism is not sensitive to Gentamicin
    Gentamicin
    Gentamicin is an aminoglycoside antibiotic, used to treat many types of bacterial infections, particularly those caused by Gram-negative organisms. However, gentamicin is not used for Neisseria gonorrhoeae, Neisseria meningitidis or Legionella pneumophila...

  • Tuberculosis
    Tuberculosis
    Tuberculosis, MTB, or TB is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis. Tuberculosis usually attacks the lungs but can also affect other parts of the body...

     in combination with other anti-TB drugs. It is not the first-line treatment, except in medically under-served populations where the cost of more expensive treatments is prohibitive.
  • Plague (Yersinia pestis
    Yersinia pestis
    Yersinia pestis is a Gram-negative rod-shaped bacterium. It is a facultative anaerobe that can infect humans and other animals....

    ) has historically been treated with it as the first-line treatment. It is approved for this purpose by the U.S. Food and Drug Administration.
  • In veterinary medicine
    Veterinary medicine
    Veterinary Medicine is the branch of science that deals with the prevention, diagnosis and treatment of disease, disorder and injury in non-human animals...

    , streptomycin is the first-line antibiotic for use against gram negative bacteria in large animals (horses, cattle
    Cattle
    Cattle are the most common type of large domesticated ungulates. They are a prominent modern member of the subfamily Bovinae, are the most widespread species of the genus Bos, and are most commonly classified collectively as Bos primigenius...

    , sheep etc.). It is commonly combined with procaine penicillin
    Penicillin
    Penicillin is a group of antibiotics derived from Penicillium fungi. They include penicillin G, procaine penicillin, benzathine penicillin, and penicillin V....

     for intramuscular injection.


While streptomycin is traditionally given intramuscular
Intramuscular injection
Intramuscular injection is the injection of a substance directly into a muscle. In medicine, it is one of several alternative methods for the administration of medications . It is used for particular forms of medication that are administered in small amounts...

ly (indeed, in many countries it is only licensed to be used intramuscularly), the drug may also be administered intravenously.

Pesticide

Streptomycin is also used as a pesticide, to combat the growth of bacteria, fungi, and algae. Streptomycin controls bacterial and fungal diseases of certain fruit, vegetables, seed, and
ornamental crops, and controls algae in ornamental ponds and aquaria. A major use is in the control of fireblight
Fireblight
Fire blight, also written fireblight, is a contagious disease affecting apples, pears, and some other members of the family Rosaceae. It is a serious concern to producers of apples and pears...

on apple and pear trees. As in medical applications, extensive use can be associated with the development of resistant strains.

Cell culture

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

Further reading

. The history behind the discovery of streptomycin.
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