Kanamycin A - WikiHQ

Kanamycin A, often referred to simply as kanamycin, is an antibiotic used to treat severe bacterial infections and tuberculosis.

Common side effects include hearing and balance problems. Kanamycin is in the aminoglycoside family of medications. It works by blocking the production of proteins that are required for bacterial survival. It was removed from the World Health Organization's List of Essential Medicines in 2019. It is no longer marketed in the United States.

Pregnancy and breastfeeding

Kanamycin is pregnancy category D in the United States.

Children

Kanamycin should be used with caution in newborns due to the risk of increased drug concentration resulting from immature kidney function. Ototoxicity is a common quality among aminoglycosides, and its rate of incidence in kanamycin is around 3-10%.

Other side effects include:

Bacterial resistance

Bacterial resistance to kanamycin is a serious and increasing phenomenon, which is very concerning for its use in treating multidrug-resistant tuberculosis and other multidrug-resistant Gram-negative bacterial infections. This is due in part to possible cross-resistance between kanamycin and other aminoglycosides, such as amikacin, capreomycin, and gentamicin. Resistance to these aminoglycosides is due to mutations in the 16S rRNA gene (rrs) within the 30S subunit that stops the antibacterial from binding tightly to the gene. These mutations are most commonly identified through a single-nucleotide variant at the position 1401.

Composition

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

The IUPAC name of Kanamycin A is O-3-amino-3-deoxy-α-D-glucopyranosyl-(1→6)-O-[6-deoxy-6-amino-α-D-glucopyranosyl-(1→4)]-2-deoxy-D-streptamine.

Biosynthesis

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.

Use in research

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 μg/mL) containing agar plates or are grown in media containing kanamycin (50-100 μg/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).

KanMX marker

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.

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.

Antibiotic Conjugated Nanoparticle Synthesis

Antibiotic resistance or development of multi-drug resistant bacterial strains is a key challenge for treating bacterial infections. With limited research being carried out to design and develop new antibiotics, novel approaches like functionalizing antibiotic to metal nanoparticles surface to treat resistant bacterial strains have been studied. Kanamycin functionalized gold-nanoparticles (Kan-GNPs) were synthesized and tested for its antibacterial activity against both gram positive and gram negative strains. A dose dependent antibacterial activity was noted for Kan-GNPs in comparison to free kanamycin.