|24-09-2022 (153 lectures)||Categoria: Streptomycin|
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|Bioavailability||84% to 88% IM (est.) 0% by mouth|
|Elimination¬†half-life||5 to 6 hours|
|CompTox Dashboard (EPA)|
|Chemical and physical data|
|Molar mass||581.580 g¬∑mol‚ąí1|
|3D model (JSmol)|
|Melting point||12¬†¬įC (54¬†¬įF)|
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Streptomycin is an¬†antibiotic medication used to treat a number of bacterial infections, including¬†tuberculosis,¬†Mycobacterium avium complex,¬†endocarditis,¬†brucellosis,¬†Burkholderia infection,¬†plague,¬†tularemia, and¬†rat bite fever. For active tuberculosis it is often given together with¬†isoniazid,¬†rifampicin, and¬†pyrazinamide. It is administered by¬†injection into a vein or¬†muscle.
Common side effects include¬†vertigo, vomiting, numbness of the face, fever, and rash. Use during¬†pregnancy may result in permanent¬†deafness in the developing baby. Use appears to be safe while¬†breastfeeding. It is not recommended in people with¬†myasthenia gravis or other¬†neuromuscular disorders. Streptomycin is an¬†aminoglycoside. It works by blocking the ability of¬†30S ribosomal subunits to make proteins, which results in¬†bacterial death.
Albert Schatz first isolated streptomycin in 1943 from¬†Streptomyces griseus. It is on the¬†World Health Organization's List of Essential Medicines. The World Health Organization classifies it as critically important for human medicine.
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¬†intravenously.
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¬†cyanobacterial 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.
Streptomycin, in combination with penicillin, is used in a standard antibiotic cocktail to prevent bacterial infection in cell culture.[medical citation needed]
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.[medical citation needed]
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) can be affected, resulting in¬†tinnitus,¬†vertigo,¬†ataxia, kidney toxicity, and can potentially interfere with diagnosis of kidney malfunction.
Common side effects include¬†vertigo, 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.
It is not recommended in people with¬†myasthenia gravis.
Streptomycin has two mechanism of action depending on what conformation (isomer) is at in the system in which it will work. Isomer A functions as a¬†protein synthesis inhibitor. It binds to the small 16S rRNA of the 30S subunit of the bacterial ribosome irreversibly, 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. Speculation on this mechanism indicates that the binding of the molecule to the 30S subunit interferes with 30S subunit association with the¬†mRNA strand. This results in an unstable ribosomal-mRNA complex, leading to a¬†frameshift mutation and premature stopping of protein synthesis; leading to cell death. As human and bacterial both have ribosomes, streptomycin has significant side effects in human cells. At low concentrations, however, streptomycin only inhibits growth of the bacteria by inducing prokaryotic ribosomes to misread mRNA.
Streptomycin isomer B is a peptidoglycan synthesis inhibitor much like lysozyme. It binds to the glycosidic linkages and breaks them through a SN2 mechanism. This leads to bacterial cell walls' integrity being compromised, ultimately resulting in death of microbial cells.
Streptomycin is an antibiotic that inhibits both Gram-positive and Gram-negative bacteria, and is therefore a useful broad-spectrum antibiotic.
Streptomycin was first isolated on October 19, 1943, by¬†Albert Schatz, a PhD student in the laboratory of¬†Selman Abraham Waksman at¬†Rutgers University in a research project funded by¬†Merck and Co. Waksman and his laboratory staff 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 cure for¬†tuberculosis (TB). In 1952 Waksman was the recipient of the¬†Nobel Prize in Physiology or Medicine 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 with hopes of starting a human clinical trial of streptomycin in tuberculosis.:‚Ää209‚Äď241 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 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.:‚Ää209‚Äď241 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.:‚Ää209‚Äď241
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. 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‚ÄĒRobert J. Dole, later Majority Leader of the United States Senate and presidential nominee‚ÄĒexperienced 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‚Äď1982). The trial was neither¬†double-blind 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.
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.