DaMocles SS 2015 Gruppe D Lukas Koser, Yannick Kristiansen, Annika Lill, Tim Maier Dozent: Prof. Dr. Wolf Dieter Fessner Streptomycin 1. Streptomycin, an Aminoglycoside Streptomycin (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-carbaldehyd; C21H39N7O13 ) is an antibiotic drug of the drug class called aminoglycosides. It is produced by different Streptomyces, which are found in soil. It is used in human medicine and sometimes it is used in agriculture against fire blight (a contagious disease triggered by Erwinia amylovora (Enterobacteriaceae)1. General Information: 2 Molecular mass:581,6 g/mol CAS Registry Number:57-92-1 GHS label: H302: Harmful if swallowed Toxicological data: LD50 (Rat, oral) 9000mg/kg 2. History On 19th October 1943 Streptomycin was first discovered by Albert Schatz , Elizabeth Bugic and Selman Maksman. Streptomycin was very useful against causative organism of tuberculosis.3 While various causative organisms could be fought with penicilin (first isolation by Alexander 1 https://de.wikipedia.org/wiki/Feuerbrand 2 https://de.wikipedia.org/wiki/Streptomycin 3 https://de.wikipedia.org/wiki/Streptomycin Fleming in 1928), there was no useful medicine against tubercolosis. This fact makes the discover of Streptomycin to a historical event. Selman Waksman was awarded with a Nobel Price for medicine in 19524. Bugie and Schatz were excluded. 3. Biosynthesis Streptomycin is produced by the bacteria Streptomyces griseus. Streptomycin consists of aminocyclitol (streptidine), 6-deoxyhexose (streptose), and N-methyl-L-glucosamine moieties, which are formed by independent biosynthetic pathways. All of them are derivated from D-Glucose. 5 Experiments on streptomycin biosynthesis in S. griseus have revealed over 29 genes involved in the pathway 6 The culture media contains : Glucose 4.0 g; Yeast extract 4.0 g; Malt extract 10.0 g; CaCO3 2.0 g; Agar 12.0 g; Distilled water 1000.0 ml.7 (Mechanism is on the last page) 4. Medical / Pharmacology The trade name of Streptomycin is STREPTO-Fatol. It is produced and marked by Riemser Pharma GmbH as a dry substance. (Registered since 12/1998)8 Streptomycin is administered as a sulft salt in sterile, distilled water or in an isotonic sodium chloride solution.9 Streptomycin is an antibiotic drug, which can be used against different types of bacteria10. Most of the time it is used as a tuberculostatica. Tubercolosis is triggered by varoius strains of mycobacteria. The most common representive is Mycobacterium Tuberculosis.11 Other applications12: : o bacterial endocarditis ( triggered by strains of Streptococcus / Enterococcus) o Brucellosis („Malta fever“, “ Mediterranean fever“ different type – triggered by the species Brucella) o Tularemia („rabbit fever“ – triggered by Francisella tularensis) o Plague (Versinia Pestis) 4 https://de.wikipedia.org/wiki/Liste_der_Nobelpreistr%C3%A4ger_f%C3%BCr_Physiologie_oder_ Medizin 5 Abgerufen 15.6.2015, from http://www.genome.jp/dbget-bin/www_bget?map00521 6 Patricia M. Flatt und Taifo Mahmud (2006): Biosynthesis of aminocyclitol-aminoglycoside antibiotics and related compounds. Aus: Natural Product Reports 2007 Apr; Vol. 24 (2), Seite 358-92. 7 Abgerufen 15.6.2015 from https://www.dsmz.de/catalogues/details/culture/dsm-40236.html ; website of The Leibniz Institute DSMZ - German Collection of Microorganisms and Cell Cultures GmbH 8 Fachinformationen bzgl STREPTO-Fatol der Fa. Riemser Pharma GmbH Stand:12/2012 “Bezeichnung des Arzneimittels” 9 Fachinformationen bzgl STREPTO-Fatol der Fa. Riemser Pharma GmbH Stand:12/2012 “Art und Dauer der Anwendung” 10 https://de.wikipedia.org/wiki/Streptomycin 11http://flexikon.doccheck.com/de/Tuberkulose?utm_source=www.doccheck.flexikon&utm_medium=web&ut m_campaign=DC%2BSearch 12http://flexikon.doccheck.com/de/Streptomycin?utm_source=www.doccheck.flexikon&utm_medium=web&ut m_campaign=DC%2BSearch Streptomycin is only used as a copreparation, becuause of the fast resistance formation against it. Generally we can say that Streptomycin is very rare in clinical application.13 For example, tubercolosis is nowdays rarely treaten with Streptomycin.14 Streptomycin works protein biosynthesis inhibiting. It binds to the small subunit (30s) of the 70s ribosome of the bacteria. As a result of it is the translation affected.15 The bacteria can’t translate proteins anymore and it can’t survive, in the ideal case . Resistances are formed fast against Streptomycint. The resistant Bacteria expressed a different ribosomal protein of the 30s subunit. Streptomycin can’t bind on this protein anymore. It is also possible, that the resistance is shown in the enzymatic cleavage of Streptomycin.16 Side effects of Streptomycin are kidney damage and hearing damange (when it is used over a period of time) - Ototoxicity and Nephrotoxic. 17 13 Fachinformationen bzgl STREPTO-Fatol der Fa. Riemser Pharma GmbH Stand:12/2012 “Anwendungsgebiete” 14 Duale Reihe- Medizinische Mikrobiologie- Herbert Hof, Rüdiger Dörries (4.Auflage) Seite 382 15 Rolf Knippers, Alfred Nordheim- Molekulare Genetik 10. Auflage Seite 256 16 Fachinformationen bzgl STREPTO-Fatol der Fa. Riemser Pharma GmbH Stand:12/2012 “Pharmakodynamische Eigenschaften- Resistenzmechanismen” 17http://flexikon.doccheck.com/de/Streptomycin?utm_source=www.doccheck.flexikon&utm_medium=web&ut m_campaign=DC%2BSearch Patricia M. Flatt and Taifo Mahmud (2006): Biosynthesis of aminocyclitol-aminoglycoside antibiotics and related compounds. In: Natural Product Reports 2007 Apr; Vol. 24 (2), pp. 358-92. .