Wednesday, 18 June 2008

How does gentamicin work?

Following on from our elucidation of penicillin's action, we now turn to another commonly-used antibiotic: gentamicin. We'll use it as our representative of the aminoglycoside class of antibiotics.

Again, it's worth reminding ourselves of the schema for the mechanisms of action of antibiotics. The three groups are:
  • Those inhibiting cell wall synthesis
  • Those inhibiting protein synthesis
  • Those inhibiting nucleic acid synthesis

Aminoglycosides inhibit protein synthesis.

Remember ribosomes? They're little factories that receive the messenger RNA (freshly transcribed from DNA) and use it as a template to construct proteins, one amino acid at a time. No protein gets made but through the hard work of a ribosome, and without proteins - and thus enzymes - life isn't possible. Not for us, and not for a bacterium. Ribosomes are essential for life.

Each ribosome is a complex of two subunits, one large and one small. The subunits that bacteria use are different from the subunits that we (as well as the rest of earthly life) use, and this provides an opening for gentamicin. It binds to the smaller of the bacterium's subunits - the unhelpfully-named 30S subunit - and thereby inhibits its functioning. And without the ability to construct proteins, the bacterium is doomed. Bad for it, good for us.

One other interesting complication deserves mention. Consensus opinion is that mitochondria are evolved from ancient bacteria that got incorporated into a eukaryotic cell more than a billion years ago. (If that doesn't surprise you, I don't know what will.) I'll write something on this fiercely interesting topic sometime soon, but the point of telling you about it is this: mitochrondria have their own ribosomes, but they are basically bacterial ones, and are thus potentially a target for gentamicin. Yet gentamicin doesn't seem to affect them. Why not? Interestingly, it appears that the double membrane that envelops our mitochondria protects them from gentamicin's power. Whew! Another close call averted...

1 comment:

  1. then how does gentamicin affect the auditory nerve?