Neomycin

[unigirl]

Why is the aminoglycoside Neomycin bactericidal to aerobic gram-negative bacteria?

[theprof]

Neomycin is a polycationic aminoglycoside produced by actinomycetes that was first isolated in 1949 from the soil-dwelling microbe Streptomyces fradiae. Isolated, neomycin is a mixture composed primarily of two stereoisomers, neomycin B and C, both of which possess antibacterial activity. In addition, there is a third component, neomycin A, that is generated by the hydrolysis of neomycins B and C. There are a number of other antibiotics which fall into the same class as neomycin, such as streptomycin, gentamycin and tobramycin

Neomycin has been used as both an oral and a topical antibiotic and is reasonably effective against most clinically important aerobic gram-negative bacteria. It has, however, only minor effects on Streptococci and gram-positive Bacilli. Its use to treat tuberculosis was discontinued years ago due to serious side effects. It has also been used in combination with niacin to decrease serum cholesterol and lipoprotein A concentrations, although once again, side effects have prevented it from being used clinically as a cholesterol-lowering agent. In the USA, Neomycin sulphate cream is widely used both as an OTC topical agent for cuts, wounds and microbial skin infections and as a preparative treatment in bowel surgery.

Aminoglycosides such as neomycin B are bactericidal in that they prevent translation of messenger RNA by prokaryotic ribosomes. RNA molecules that recognize neomycin share a common stem-loop structural motif. Studies have shown that aminoglycosides inhibit protein synthesis by direct interaction with the ribosomal RNA. Aminoglycosides such as neomycin bind to the A site of rRNA, which is the entry site for aminoacyl tRNAs. Binding of the aminoglycoside interferes with protein synthesis by causing codon misreading. The translational block may arise from stabilization of a unique high-affinity conformation of rRNA in the tRNA�mRNA complex, thereby disturbing the accuracy of protein synthesis.

[theprof]

I should have pointed out that it's the 30S subunit that is affected by neomycin and other aminoglycosides. The codon misreading hinders translation, resulting in shortened chains which eventually leads to disabled ribosomes.

Anaerobic bacteria and Streptococci are largely resistant to Aminoglycosides as they do not possess the necessary transport molecules.