Kanamycin A

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Not to be confused with kanamycin B.
Kanamycin A
Kanamycin A.svg
Clinical data
AHFS/Drugs.com Monograph
Pregnancy
category
  • D
Routes of
administration
By mouth, intravenous, intramuscular
ATC code A07AA08 (WHO) J01GB04 (WHO) S01AA24 (WHO)
Legal status
Legal status
  •  ?
Pharmacokinetic data
Bioavailability very low after by mouth delivery
Metabolism Unknown
Biological half-life 2 hours 30 minutes
Excretion Urine (as unchanged drug)
Identifiers
CAS Number 59-01-8 YesY
PubChem (CID) 6032
DrugBank DB01172 YesY
ChemSpider 5810 YesY
UNII RUC37XUP2P YesY
ChEBI CHEBI:17630 YesY
ChEMBL CHEMBL1384 YesY
PDB ligand ID KAN (PDBe, RCSB PDB)
Chemical and physical data
Formula C18H36N4O11
Molar mass 484.499
3D model (Jmol) Interactive image
  (verify)

Kanamycin A, also known as kanamycin, is an antibiotic used to treat severe bacterial infections and tuberculosis. It is not a first line treatment. It is used by mouth, injection into a vein, or injection into a muscle. Kanamycin is recommended for short-term use only, usually from 7 to 10 days. It is not effective in viral infections.[1]

Common side effects include hearing and balance problems. Kidney problems may also occur. Kanamycin is not recommended during pregnancy as it may harm to the baby.[1] It is likely safe during breastfeeding.[2] Kanamycin is in the aminoglycoside family of medications. It works by blocking the production of proteins that are required for bacterial survival.[1]

Kanamycin was first isolated in 1957 by Hamao Umezawa from the bacterium Streptomyces kanamyceticus.[1][3] It is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system.[4] The wholesale cost in the developing world is 0.85 to 1.52 USD per dose as of 2014.[5] It is no longer commercially avaliable in the United States.[1]

Medical uses[edit]

Spectrum of activity[edit]

Kanamycin is indicated for short term treatment of bacterial infections caused by one or more of the following pathogens: E. coli, Proteus species (both indole-positive and indole-negative), Enterobacter aerogenes, Klebsiella pneumoniae, Serratia marcescens, and Acinetobacter species. In cases of serious infection when the causative organism is unknown, Kanamycin injection in conjunction with a penicillin- or cephalosporin-type drug may be given initially before obtaining results of susceptibility testing.

Kanamycin does not treat viral infections.[6]

Pregnancy and breastfeeding[edit]

Kanamycin is pregnancy category D in the United States.[6]

Kanamycin is enters breast milk in small amounts. The manufacturer therefore advises that people should either stop breastfeeding or kanamycin. The American Academy of Pediatrics considers kanamycin okay in breastfeeding.[7]

Children[edit]

Kanamycin should be used with caution in newborns due to the risk of increased drug concentration resulting from immature kidney function.[6]

Side effects[edit]

Serious side effects include ringing in the ears or loss of hearing, toxicity to kidneys, and allergic reactions to the drug.[8]

Other side effects include:[6]

Gastrointestinal effects

  • Nausea, vomiting, diarrhea

Musculoskeletal effects

  • Myasthenia gravis

Neurologic effects

  • Headache
  • Paresthesias
  • Blurring of vision
  • Neuromuscular blockade

Metabolic effects

  • Malabsorption syndrome

Mechanism[edit]

Kanamycin interacts with the 30S subunit of prokaryotic ribosomes. It gives birth to substantial amounts of mistranslation and indirectly inhibits translocation during protein synthesis.[9][10]

Kanamycin works by interfering with protein synthesis. It binds to the 30S subunit of the bacterial ribosome. This results in incorrect alignment with the mRNA and eventually leads to a misread that causes the wrong amino acid to be placed into the peptide. This leads to nonfunctional peptide chains.[11]

Composition[edit]

Kanamycin is a mixture of three main components: kanamycin A, B, and C. Kanamycin A is the major component in kanamycin.[12] The effects of these components do not appear to be widely studied as individual compounds when used against prokaryotic and eukaryotic cells.

Biosynthesis[edit]

While the main product produced by Streptomyces kanamyceticus is kanamycin A, additional products are also produced, including kanamycin B, kanamycin C, kanamycin D and kanamycin X.

The kanamycin biosynthetic pathway can be divided into two parts. The first part is common to several aminoglycoside antibiotics, such as butirosin and neomycin. In it a unique aminocyclitol, 2-deoxystreptamine, is biosynthesized from D-glucopyranose 6-phosphate in four steps. At this point the kanamycin pathway splits into two branches due to the promiscuity of the next enzyme, which can utilize two different glycosyl donors - UDP-N-acetyl-α-D-glucosamine and UDP-α-D-glucose. One of the branches forms kanamycin C and kanamycin B, while the other branch forms kanamycin D and kanamycin X. However, both kanamycin B and kanamycin D can be converted to kanamycin A, so both branches of the pathway converge at kanamycin A.[13]

Use in research[edit]

Kanamycin is used in molecular biology as a selective agent most commonly to isolate bacteria (e.g., E. coli) which have taken up genes (e.g., of plasmids) coupled to a gene coding for kanamycin resistance (primarily Neomycin phosphotransferase II [NPT II/Neo]). Bacteria that have been transformed with a plasmid containing the kanamycin resistance gene are plated on kanamycin (50-100 ug/ml) containing agar plates or are grown in media containing kanamycin (50-100 ug/ml). Only the bacteria that have successfully taken up the kanamycin resistance gene become resistant and will grow under these conditions. As a powder, kanamycin is white to off-white and is soluble in water (50 mg/ml).

At least one such gene, Atwbc19[14] is native to a plant species, of comparatively large size and its coded protein acts in a manner which decreases the possibility of horizontal gene transfer from the plant to bacteria; it may be incapable of giving resistance to bacteria even if gene transfer occurs.

KanMX marker[edit]

The selection marker kanMX is a hybrid gene consisting of a bacterial aminoglycoside phosphotransferase (kanr from transposon Tn903) under control of the strong TEF promoter from Ashbya gossypii.[15][16]

Mammalian cells, yeast, and other eukaryotes acquire resistance to geneticin (= G418, an aminoglycoside antibiotic similar to kanamycin) when transformed with a kanMX marker. In yeast, the kanMX marker avoids the requirement of auxotrophic markers. In addition, the kanMX marker renders E. coli resistant to kanamycin. In shuttle vectors the KanMX cassette is used with an additional bacterial promoter. Several versions of the kanMX cassette are in use, e.g. kanMX1-kanMX6. They primarily differ by additional restriction sites and other small changes around the actual open reading frame.[15][17]

References[edit]

  1. ^ a b c d e "Kanamycin Sulfate". The American Society of Health-System Pharmacists. Retrieved 6 December 2016. 
  2. ^ "Kanamycin (Kantrex) Use During Pregnancy". www.drugs.com. Retrieved 7 December 2016. 
  3. ^ Sneader, Walter (2005). Drug Discovery: A History. John Wiley & Sons. p. 302. ISBN 9780471899792. 
  4. ^ "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014. 
  5. ^ "Kanamycin Sulfate". International Drug Price Indicator Guide. Retrieved 7 December 2016. 
  6. ^ a b c d "Kanamycin (By injection)". 
  7. ^ Briggs, Gerald (2011). Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk. Lippincott Williams & Wilkins. p. 787. 
  8. ^ Consumer Drug Information: Kanamycin, 2 April 2008, retrieved 2008-05-04 
  9. ^ Pestka, S.: "The Use of Inhibitors in Studies on Protein Synthesis", Methods in Enzymology 30, pp.261-282, 1975
  10. ^ Misumi, M. & Tanaka, N.: "Mechanism of Inhibition of Translocation by Kanamycin and Viomycin: A Comparative Study with Fusidic Acid, Biochem.Biophys.Res.Commun. 92, pp.647-654, 1980
  11. ^ DrugBank, ed. (2016-08-17). "Kanamycin". DrugBank. 
  12. ^ United States. National Institutes of Health. Kanamycin Compound Summary. PubChem. Web. 21 Aug. 2012.
  13. ^ "kanamycin biosynthesis pathway in MetaCyc". MetaCyc.org. Retrieved 30 September 2014. 
  14. ^ "Horizontal Gene Transfer: Plant vs. Bacterial Genes for Antibiotic Resistance Scenario's—What's the Difference?". Isb.vt.edu. Retrieved 2013-06-24. 
  15. ^ a b Wach, A.; Brachat, A.; Pöhlmann, R.; Philippsen, P. (1994). "New heterologous modules for classical or PCR-based gene disruptions in Saccharomyces cerevisiae". Yeast. 10 (13): 1793–1808. doi:10.1002/yea.320101310. PMID 7747518. 
  16. ^ Steiner, S.; Philippsen, P. (1994). "Sequence and promoter analysis of the highly expressed TEF gene of the filamentous fungus Ashbya gossypii". Molecular & general genetics : MGG. 242 (3): 263–271. doi:10.1007/BF00280415. PMID 8107673. 
  17. ^ Wach, A. (1996). "PCR-synthesis of marker cassettes with long flanking homology regions for gene disruptions in S. Cerevisiae". Yeast. 12 (3): 259–265. doi:10.1002/(SICI)1097-0061(19960315)12:3<259::AID-YEA901>3.0.CO;2-C. PMID 8904338. 

External links[edit]