Streptomycin

drugbox
IUPAC_name = 5-(2,4-diguanidino-
3,5,6-trihydroxy-cyclohexoxy)- 4- [4,5-dihydroxy-6-(hydroxymethyl)
-3-methylamino-tetrahydropyran-2-yl] oxy-3-hydroxy-2-methyl
-tetrahydrofuran-3-carbaldehyde

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CAS_number = 57-92-1
ATC_prefix = A07
ATC_suffix = AA04
ATC_supplemental = ATC|J01|GA01
PubChem = 5999
DrugBank = APRD00412
C=21 | H=39 | N=7 | O=12
molecular_weight = 581.574 g/mol
smiles =
melting_point = 12
bioavailability = 84% to 88% (est.)" [http://www.medscape.com/viewarticle/409778_4 Streptomycin in Patients with Tuberculosis] ." "Pharmacotherapy" 21(9):1037-1045, 2001. Retrieved on July 7, 2008.]
metabolism =
elimination_half-life = 5 to 6 hours
excretion = Renal
pregnancy_category = D" [http://drugsafetysite.com/streptomycin Streptomycin in pregnancy and breastfeeding: Drug safety] ." "Drug Safety Site", 2006. Retrieved on July 7, 2008.]
routes_of_administration = Intramuscular, intravenous
legal_US = Rx-only
legal_UK = POM
width = 208

Streptomycin is an antibiotic drug, the first of a class of drugs called aminoglycosides to be discovered, and was the first antibiotic remedy for tuberculosis. It is derived from the actinobacterium "Streptomyces griseus". Streptomycin is a bactericidal antibioticcite journal | quotes = no | author = Singh B., Mitchison, D.A. | year = 1954 | title = Bactericidal activity of streptomycin and isoniazid against tubercle bacilli | journal = British Medical Journal | volume = 1 | issue = 4854 | pages = 130-2 | id = PMID 13106497 | url = http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=13106497] . It kills sensitive microbes by hurting cell membranes and inhibiting protein synthesis. Specifically, it binds to the 16S rRNA of the bacterial ribosome, interfering with the binding of formyl-methionyl-tRNA to the 30S subunit. This prevents initiation of protein synthesis and leads to death of microbial cells. Humans have structurally different ribosomes from bacteria, thereby allowing the selectivity of this antibiotic for bacteria. Streptomycin cannot be given orally, but must be administered by regular intramuscular injection. An adverse effect of this medicine is ototoxicity. It can result in temporary hearing loss.

History

It was first isolated on October 19 1943 by Albert Schatz, a graduate student, in the laboratory of Selman Abraham Waksman at Rutgers University. Waksman and his laboratory discovered several antibiotics, including actinomycin, clavacin, streptothricin, streptomycin, grisein, neomycin, fradicin, candicidin and candidin. Of these, streptomycin and neomycin found extensive application in the treatment of numerous infectious diseases. Streptomycin was the first antibiotic that could be used to cure the disease tuberculosis; early production of the drug was dominated by Merck & Co. under George W. Merck.

The first randomized trial of streptomycin against pulmonary tuberculosis was carried out in 1947 by the MRC Tuberculosis Research Unit. Whilst neither double-blind nor placebo-controlled, and as such not a perfectly fair trial, results showed efficacy against TB, albeit with minor toxicity and acquired bacterial resistance to the drug. [ [http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1116443 A change in scientific approach: from alternation to randomised allocation in clinical trials in the 1940s] (retrieved 2008-09-27)]

Uses

Treatment of disease

* Tuberculosis in combination with other anti-TB drugs. It is not the first line treatment.
* Plague ("Yersinia pestis") has historically been treated with it as the first line treatment. It is approved for this purpose by the U.S. FDA.
* Infective endocarditis caused by enterococcus when the organism is not sensitive to Gentamicin
* In veterinary medicine, streptomycin is the first line antibiotic for use against gram negative bacteria in large animals (horses, cattle, sheep etc.). It is commonly combined with procaine penicillin for intramuscular injection.

Bacterial selection experiments

When grown on medium containing streptomycin, bacteria such as "Escherichia coli" are dependent upon expression of the "aadA" gene in order to survive (Joung "et al.", 2000). Thus, a suitably engineered "E. coli" strain, can be combined with a streptomycin-doped medium to select only bacteria hosting a successful interaction in two-hybrid screening experiments and methods derivative of two-hybrid screening (Hurt "et al.", 2003; Joung "et al.", 2000) Streptomycin is an antibiotic that inhibits both gram positive and gram negative bacteria, and is a therefore a useful broad spectrum antibiotic.

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, andornamental crops, and controls algae in ornamental ponds and aquaria. 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.

ee also

*Neomycin
*Philip D'Arcy Hart

Footnotes

References

*Hurt, J. A., S. A. Thibodeau, A. S. Hirsh, C. O. Pabo and J. K. Joung (2003). "Highly specific zinc finger proteins obtained by directed domain shuffling and cell-based selection." Proc Natl Acad Sci U S A 100(21): 12271-6.
*Joung, J. K., E. I. Ramm and C. O. Pabo (2000). "A bacterial two-hybrid selection system for studying protein-DNA and protein-protein interactions." Proc Natl Acad Sci U S A 97(13): 7382-7.
*Kingston, William (2004). [http://jhmas.oxfordjournals.org/cgi/content/abstract/59/3/441 Streptomycin, Schatz v. Waksman, and the Balance of Credit for Discovery] . "Journal of the History of Medicine and Allied Sciences" 59 (3), 441-462.
*Mistiaen, Veronique. [http://www.guardian.co.uk/weekend/story/0,3605,823114,00.html Time, and the great healer] . The Guardian, Saturday 2 November 2002. The history behind the discovery of streptomycin.
*Lawrence, Peter A. (2002). [http://www.nature.com/cgi-taf/DynaPage.taf?file=/nature/journal/v415/n6874/full/415835a_fs.html The misallocation of credit is endemic in science] . "Nature" 415 (6874), 835-836.
* [http://www.epa.gov/oppsrrd1/REDs/factsheets/0169fact.pdf EPA R.E.D. Facts sheet] on use of streptomycin as a pesticide.