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New weapon against antibiotic resistance

Wednesday, 19 March 2008
Cosmos Online
New weapon against antibiotic resistance

Resistance movement: A model of the MurM enzyme. Individual amino acid residues are represented as spheres. This image represents MurM from a penicillin-resistant strain of Streptococcus. The amino acid residues coloured blue are different in penicillin-sensitive Streptococcus.

Credit: University of Warwick

BRISBANE: Antibiotic-resistant bacteria, such as MRSA, are a huge and growing threat to our ability to fight infection. But now microbiologists have discovered a weak link in the armour of these dangerous pathogens.

Another bacterium, Streptococcus pneumoniae, kills five million children per year worldwide, and is becoming increasingly difficult to treat due to drug resistance. Australian rates of penicillin resistance in S.pneumoniae rose from one per cent to 25 per cent between 1989 and 1997.

Turning off resistance

Now experts at the University of Warwick in the U.K. have taken a step forward in the fight against this killer by revealing just how it is able to develop resistance to the antibiotic penicillin, and how we can turn this resistance off.

Penicillin achieves its antibiotic effect by preventing bacteria from producing essential building blocks of their cell walls, known as peptidoglycans. This wall is a protective shell that both protects and holds a bacterial cell in shape, so removing it kills the cells and renders them unable to replicate.

Penicillin-resistant bacteria have mutated forms of cell wall proteins that don't allow penicillin to bind, making the drug much less useful. Now, researchers led by Warwick's Adrian Lloyd have discovered exactly how this resistance is built using an enzyme called MurM.

As they report in the March Journal of Biological Chemistry Lloyd's team discovered that MurM builds special protein bridges in the cell wall. When the enzyme is removed the bacteria are unable to build these bridges and they lose their resistance to penicillin.

Understanding enzymology

To make the discovery, his team recreated the MurM catalysed reaction in a test tube, which allowed them to study each step of the process in detail. Defining each step in the reaction has given clues to many potential drug options to disrupt the process.

"Because we now understand the enzymology of this step catalysed by MurM, we should be able to design inhibitors to MurM that could restore penicillin sensitivity," said Lloyd. He believes that a drug which blocks the action of the enzyme may also be effective against other drug-resistant strains of bacterium.

Methicillin-resistant Staphylococcus aureus, or MRSA, the bacterium that has wreaked havoc in hospitals worldwide, achieves its resistance in a similar way to Streptococcus pneumoniae, and is therefore a prime candidate to focus on, said the researchers.

MRSA clues

"The MurM gene is strongly conserved across a variety of [pathogens] including MRSA," agreed microbiologist John Pemberton at the University of Queensland in Brisbane, Australia. Pemberton, who was not involved in the study, says that findings could have implications for treating a wide range of antibiotic resistant bacteria.

Peter Collignon, who studies infectious diseases at the Australian National University in Canberra, said the next step of finding drugs that are effective against possible targets is a tricky one, but commends the study for flagging a number of possible avenues to explore.

"The reality is that only a small percentage of targets actually payoff and that's why we need lots of potential targets like those described in this study," he said.

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Readers' comments

It’s indeed a great

It’s indeed a great miracle that the amazing antibiotic penicillin was discovered.
May be the effective ness of the antibiotic lasted for few years and pathogens stated showing resistance.
In spite of so many newer molecules in the field of infection, antibiotics resistance also is acquired at a faster rate .
The pathogens are so intelligent that they are using various techniques like plasmid mediated , through re organizing chromosome, effusion pump like action to throw away anti biotic collected in them while therapy being given and may be some thing in a better way organized to win over the modern scientist and his experiments.
Can we really STOP IT ????? A Billon $ Question...
TALLURI VIJAI KUMAR

waste of time, try colloidal silver

antibiotics are redundant anyway:
http://www.all-natural.com/silver-1.html

I am glad that you can read

I am glad that you can read and believe a 2nd rate, tacky website when it comes to your health. Since 2 doctors in the 1970's thought silver was a good idea that MUST mean that it is completely safe and effective.

Please note: 1970's they had no clue what even caused AIDS. You wouldn't trust a science book from the 1970's, why would you trust 2 doctors that did absolutely no studies to prove their viewpoint.