New antibiotics could come from a DNA binding compound that kills bacteria in 2 minutes

Jun 09, 2009

(PhysOrg.com) -- A synthetic DNA binding compound has proved surprisingly effective at binding to the DNA of bacteria and killing all the bacteria it touched within two minutes. The DNA binding properties of the compound were first discovered in the Department of Chemistry at the University of Warwick by Professor Mike Hannon and Professor Alison Rodger (Professor Mike Hannon is now at the University of Birmingham). However the strength of its antibiotic powers have now made it a compound of high interest for University of Warwick researchers working on the development of novel antibiotics.

Dr Adair Richards from the University of Warwick said:

"This research will assist the design of new compounds that can attack bacteria in a highly effective way which gets around the methods bacteria have developed to resist our current antibacterial drugs. As this antibiotic compound operates by targeting DNA, it should avoid all current resistance mechanisms of multi-resistant bacteria such as MRSA."

The compound [Fe2L3]4+ is an iron triple helicate with three organic strands wrapped around two iron centres to give a helix which looks cylindrical in shape and neatly fits within the major groove of a DNA helix. It is about the same size as the parts of a protein that recognise and bind with particular sequences of DNA. The high positive charge of the compound enhances its ability to bind to DNA which is negatively charged.

When the iron-helicate binds to the major groove of DNA it coils the DNA so that it is no longer available to bind to anything else and is not able to drive biological or chemical processes. Initially the researchers focused on the application of this useful property for targeting the DNA of as it could bind to, coil up and shut down the cancer cell's DNA either killing the cell or stopping it replicate. However the team quickly realised that it might also be a very clever way of targeting drug-resistant bacteria.

New research at the University of Warwick, led by Dr Adair Richards and Dr Albert Bolhuis, has now found that the [Fe2L3]4+ does indeed have a powerful effect on bacteria. When introduced to two test bacteria Bacillus subtilis and E. coli they found that it quickly bound to the bacteria's DNA and killed virtually every cell within two minutes of being introduced - though the concentration required for this is high.

Professor Alison Rodger, Professor of Biophysical Chemistry at the University of Warwick, said:

"We were surprised at how quickly this compound killed bacteria and these results make this compound a key lead compound for researchers working on the development of novel antibiotics to target drug resistant bacteria."

The researchers will next try and understand how and why the compound can cross the bacteria cell wall and membranes. They plan to test a wide range of compounds to look for relatives of the iron helicate that have the same mechanism for action in collaboration with researchers around the world.

Source: University of Warwick (news : web)

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User comments : 9

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mongander
not rated yet Jun 09, 2009
I hope it can be tailored to destroy only harmful bacteria.

It's anticancer mechanism sounds similar to that of artemisinin.
fuzz54
not rated yet Jun 09, 2009
For people that have resistant infections I don't think they'd care if it was good or bad bacteria that got squished as long as they can be cured. Of course you are right that the goal is only harmful bacteria.
iledius
not rated yet Jun 09, 2009
Sounds good, altough they still need to find a way to target bacteria specifically with the iron-helicate compound. As it is now, it seems that the compound can penetrate cell and nucleus membranes and target the hosts DNA just as well.
DougCollins
not rated yet Jun 09, 2009
Since mitochondrial DNA is similar to bacterial DNA, are mitochondria at risk of being attacked by the binding compound too?
nkalanaga
not rated yet Jun 09, 2009
That would be my worry as well. How do you keep it out of your own cells? I can see that there could be a difference between the cell walls of bacteria and mammalian cells that would make it work, but normal and cancerous cells in the same organism should have very similar walls.
Sean_W
1 / 5 (1) Jun 10, 2009
Does the needed specificity have something to do with the ability of the more free bacterial DNA to bind while our DNA is already coiled around chromomeres?
nkalanaga
not rated yet Jun 10, 2009
That's possible.
PPihkala
not rated yet Jun 11, 2009
I also would like more information about it's effect to host cells. It's less useable if it kills everything. Maybe for killing bacteria in foods, where it does not matter if you kill everything having a DNA. But as a drug in people, it has to be safe towards human cells and preferably to kill only harmful bacteria.
nkalanaga
not rated yet Jun 11, 2009
The latter could be a problem, as many harmful bacteria are very closely related to harmless or beneficial varieties. That's one of the problems with any antibiotic, though, so this shouldn't be any worse.

I like the idea of using it in food, as long as the residue won't be harmful if swallowed. If safe, it would be of great benefit for processed and packaged foods.