Antibiotics mechanism of action. Lessons.

MIT and Boston University researchers have discovered that while antibiotics attack many parts of bacteria cells, it is the damage they cause to their DNA that inflicts the fatal blow. … It is astonishing that we have been using antibiotics like penicillin for over 70 years, yet we did not know the exact mechanism by which they kill bacteria, until now.

In 2007, Collins discovered that three types of antibiotic, the quinolones, the beta-lactams and the aminoglycosides, all kill cells by producing hydroxyl radicals, highly destructive molecules that appear to attack just about any cell components that stand in their way: they attack lipids, they oxidize proteins, and they oxidize DNA.

But in this latest study, they found that most of this damage is not fatal.

The deadly blow is hydroxyl-induced damage to guanine, one of the four nucleotides or building blocks of DNA.

The researchers found that when they inserted damaged (ie oxidized) guanine into DNA, the cells try to repair the damage, but instead this speeds up their own death.

Corresponding author Dr Graham Walker, MIT Professor of Biology, said the mechanism isn't behind all the killing, but it appears to be responsible for a major part of it.

I can see here a couple of very interesting issues:

1.       Three types of antibiotic, the quinolones, the beta-lactams and the aminoglycosides work unselectively in the same manner by producing free radicals (everybody understands that ROS action is absolutely unselective). It simply means that the vicious lock-key (targeting) approach is not relevant even in the development of new antibiotics! Well, this is unexpectedly even for me…

2.       Evidence based medicine approach work in action: in the end of the day who cares about the mechanism of the action of a drug? Is it important for a patient dying from pneumonia that beta-lactams and quinolones may have the similar mode of action due to they produce ROS?

I think that majority of the drugs out there work in unknown way – nobody knows exactly why they are active. For sure, it would be interesting to understand the mechanism and this understanding will be probably useful in the development of novel medicines and for that we have to try to develop new approaches and accept that “retro” lock-key paradigm is over. Forever.