Heard a really nice seminar by an eminent scientist, Dr. Alexander Mankin about how antibiotics have evolved and how they work. Want to jot down a few things that I learnt from it before I forget.

For those who don’t think about this everyday, here is some background. The basic paradigm of biology is:

DNA ==Transcription==> RNA ==Translation==> Protein

All the genetic information is stored in DNA, it is transcribed into RNA, and then translated to proteins that actually do the biochemical reactions necessary for life-functions. One copy of RNA can be used multiple times to make many copies of protein.

Some of the RNA is also catalytic, but mostly it works as a molecule that carries information for translation into protein. The most important catalytic RNA is in the protein synthesizing machineary, Ribosome.

Why target ribosome for antibiotic action? Synthesis of proteins is an essential task for any living being, so, targeting it, is an obvious choice for killing an organism. But, the major problem is selectivity. All ribosomes are evolved from a common ancestor and hence it is very similar across different species. The ideal chemical should target protein synthesis of the unwanted organism but, should not affect the host (fungi or human) protein synthesis. This makes it difficult to keep making newer and newer antibiotics. Although, the current antibiotics take advantage of minute differences between the structures of human and bacterial ribosomes to be effective, they suffer from side effects due to the similarities.

Why do antibiotics work as well as they do? There has been a lot of effort in mapping the sites on ribosome where the antibiotics interact. Most of the antibiotics interact with the RNA part of ribosome. The reason behind this is very clever.

About 2/3rd of ribosome consists of RNA. There are about 10,000 ribosomes in a given bacterial cell. To make that many ribosomes, there are multiple copies of genes coding for ribosomal RNA, but, a single copy of genes coding for the protein. Because, the cell has to go through multiple steps of transcription to make enough RNA, but, a single step transcription can be followed by multiple step translation can make enough protein to assemble all these 10,000 ribosomes.

This makes it possible for a mutation in the single copy of the protein gene to disrupt its interaction with the antibiotic and make the bacteria resistant to the antibiotic. But, a mutation in one of the copies of ribosomal RNA, can make only a small fraction of functional ribosomes immune from antibiotic action and that is not enough for the bacteria to survive. Thus, molecules that interact with RNA part of ribosome to stop protein synthesis are more effective in killing bacteria.