Streptomycin isolation

Of the eight aminoglycosides that are currently used, five are synthesized from different versions of Streptomyces streptomycin (isolated from Streptomyces griseus), neomycin (isolated from Streptomyces fradiae), paromomycin (isolated from S. rimosus), kanamycin (isolated from Streptomyces kanamyceticus), and tobramycin (isolated from... 

Waksman, S.A. (1951) Streptomycin, isolation, properties, and utilization. Journal of The History of Medicine and Allied Sciences, 6, 318-347. 

Antibiotics. The genes involved in the synthesis of a variety of antibiotics have been isolated (34,35). These include antibiotics such as erythromycin, streptomycin, and also peptide antibiotics such as gramicidin and tyrocidin. Characterization of these gene products facUitates the design of novel antibiotics. In addition, overexpression of some of these gene products is also expected to improve the yield of the antibiotic (34,35). 

In 1939 the isolation of a mixture of microbial products named tyrotbricin from a soil bacillus was described. Further investigation showed this material to be a mixture of gramicidin and tyrocidine. In rapid succession the isolation of actinomycin (1940), streptothricin (1942), streptomycin (1943), and neomycin (1949), produced by Streptomjces were reported and in 1942 the word antibiotic was introduced. Chloramphenicol, the first of the so-called broad spectmm antibiotics having a wide range of antimicrobial activity, was discovered in 1947. Aureomycin, the first member of the commercially important tetracycline antibiotics, was discovered in 1948. 

Dihydrostreptomycin sulfate may be prepared from streptomycin sulfate by catalytic hydrogenation (Merck, Pfizer, Cyanamid), electrolytic reduction (Schenley, Olin Mathieson), or by sodium boro hydride reduction (Bristol), or by isolation from a fermentation process (Takeda). 

Stiepton dn was isolated by Waksman in 1944, and its activity against M tuberculosis ensured its use as a primaiy ding in the treatment of tuberculosis. Unfortunately, its ototoxicity and the rapid development of resistance have tended to modify its usefulness, and although it still remains a front-hne dmg against tuberculosis it is usually used in combination with isoniazid and p(4)-aminosalicyhc acid (section 11.5). Streptomycin also shows activity against other types of bacteria,... 

There has been isolated an analog of streptomycin which contains one more hydroxyl group67 68 and is called hydroxystreptomycin. The biological properties of this compound are closely similar to, or identical with, those of streptomycin.69... 

First among the aminoglycosides was streptomycin, one of several antibiotics isolated from Streptomyces species by Selman Waksman—this from S. griseus in 1944. Waksman proved to be an enormously effective seeker of antibiotics in natural products. In addition to streptomycin, he discovered neomycin, another widely used antibiotic. Less important discoveries include actinomycin, clavacin, streptothricin, grisein, fradicin, and candidin. Waksman received the Nobel Prize in Physiology or Medicine in 1952. 

A senior British government veterinarian stated in 1962 (3)> When penicillin was first used in treating mastitis only 2% of the strains of staphylococci recovered from cases of mastitis were resistant to penicillin. Today the figure is over 70%. Between 1958 and 1961, resistance to penicillin (PEN) increased from 62.0% to 70.6%. Resistance to streptomycin (STR), tetracycline and chloramphenicol also increased (. Antibiotic resistance increased for isolates of both mastitis staphylococci and streptococci in Canada between I960 and 1967 (5). In Belgium (6), Staphylococcus aureus strains isolated from cases of bovine mastitis showed increase in PEN resistance from 38% in 1971 to 78% in 1974> but then no further increase to 1980. The resistance situation was reported to remain stable in the Federal Republic of Germany between 1962 and 1975 (7), as also in Australia between 1974 and 1979 (8 ) and Denmark, at a very low level, for the period 1963 to 1978 (9). 

Although streptomycin was not the first antibiotic (penicillin, a fungal product, had been isolated some years earlier), its discovery was a landmark in antibiotic history. It was the first effective therapeutic for tuberculosis, a disease that had terrorized humans for cenmries and a cause of human morbidity and mortality unmatched by wars or any other pestilence. Streptomycin was the first aminoglycoside to be identified and characterized and is noteworthy in being the first useful antibiotic isolated from a bacterial source. At the present time, the use... 

Selman Waksman s commitment to the isolation and screening of soil bacteria in the search for bioactive small molecules, especially potential antibiotics, was validated by the discovery of streptomycin. This led to the creation of the modem biopharmaceutical industry and the subsequent isolation of tens of thousands of bioactive small molecules from soil bacteria and other environments. A proportion of these compounds have become highly successfnl therapeutics, not only for all types of infectious diseases, but also in the treatment of many other human and animal ailments and as anticancer, immnno-modnlatory, and cardiovascular agents. Waksman and Fleming could be considered the fathers of chemical biology (Figure 1.1). 

Streptomycin Streptomycin, fran5-2,4-diguanidino-3,5,6-trihydroxycyclohexyl-5-deoxy-2-0-(2-deoxy-2-methylamino-a-L-glucopyranosyl)-3-C-hydroxymethyl- 8-L-lyxo-pentofura-noside (32.4.1), is isolated from a culture liquid of the vital activity of the actinomycete S. griseus [238-247]. 

Aminoglycosides streptomycin (first isolated from Streptomyces griseus (Krainsky) Waksman et Henrici, Bact. isolated from unspecified manured field soil Schatz 1944 MI)... 

Penicillin plus streptomycin is effective for enterococcal endocarditis and 2-week therapy of viridans streptococcal endocarditis. Gentamicin has largely replaced streptomycin for these indications. Streptomycin remains a useful agent for treating enterococcal infections, however, because approximately 15% of enterococcal isolates that are resistant to gentamicin (and therefore to netilmicin, tobramycin, and amikacin) will be susceptible to streptomycin. 

The poly (ribitol phosphate) synthetase and poly (glycerol phosphate) synthetase are inhibited by vancomycin, novobiocin, and Crystal Violet. Other antibiotic substances which interfere with cell-wall synthesis (such as bacitracin, ristocetin, and streptomycin) are almost without effect on the isolated synthetases, and penicillin is inhibitory at high concentrations only. Moreover, penicillin, vancomycin, and bacitracin do not markedly inhibit synthesis of cell-wall glycosaminopeptide in vitro, although the synthetical activity of extracts of cells which have been pretreated with these antibiotics is lowered.Convincing evidence that the primary site of inhibition by antibiotics is the biosynthesis of cell-wall material has been obtained only for the penicillins and cycloserine, and it appears that the action of even those antibiotics may be more complex than was originally supposed. 

Acler Actiluatics. Other antibiotics were quickly discovered after the introduction of penicillin. A different type of antibiotic, streptomycin, which is active against a widei lange of pathogens than penicillin and is a potent inhibitor of Mycobacterium tuberculosis, was isolated from a strain of actinomycete from the throat of a chicken by Waksman at Rutgers in 1944 (Aiba and Evans). Actinomycetes are commonly found in soil and are intermediate between fungi and bacteria. Since 1944. numerous other metabolic products of actinomycetes have been isolated and have made a transition from the bench scale to wide therapeutic use. 

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