International prize for Cork lecturer

The search is on for a new type of antibiotic produced by the bacteria that give us cheese and yoghurt, writes Dick Ahlstrom.

The search is on for a new type of antibiotic produced by the bacteria that give us cheese and yoghurt, writes Dick Ahlstrom.

Dairy products may provide a source for the next generation of antibiotics. The great advantage of these substances is we already know they are safe, we have been eating them for centuries.

We need new antibacterial substances to replace those being overtaken by bacterial resistance. The bacteria that thrive in fermented milk products already produce these substances and the search is on by labs around the world to isolate and test these naturally occurring chemicals.

An important international prize went last week to a young University College Cork scientist who is deeply involved in this research effort.

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Dr Paul Cotter won the 2008 WH Pierce Memorial Prize for his work on discovering new bacteriocins for use against difficult organisms such as the hospital superbug MRSA, Listeria and Streptococcus.

The international prize is given each year to a microbiologist under 40 years of age who has made a substantial contribution to the science. Microbiology specialist manufacturer Oxoid Ltd sponsors the prize.

Cotter lectures in the Department of Microbiology and is a principal investigator receiving funding from Science Foundation Ireland, from the Health Research Board and from Enterprise Ireland.

The good bacteria that cause fermentation in the production of cheese and yoghurt have evolved ways of protecting themselves from harmful bacteria. They release a range of bacteriocins that are toxic to invading bacteria, and it is this action against harmful organisms that attracts scientific interest.

"The thing I focus on most is work on small proteins called peptides, produced by the safe bacteria found in cheese and yoghurt," Cotter explains.

Some of the peptides have powerful antimicrobial activity and these hold promise in the fight against antibiotic resistant organisms, he says.

The search for these peptides is not new and some are already on the market. Nisin is one of the best known and has been approved for use in food by the US Food and Drug Administration, by the World Health Organisation and the EU. It is already in use as a food-preservative in more than 50 countries, he says.

Nisin is one of a group of bacteriocins known as "lantibiotics", or lanthionine- containing antibiotics, Cotter explains. "We are looking to take advantage of their long history of safe use and powerful antimicrobial activity."

He and collaborators Prof Colin Hill of UCC's Alimentary Pharmabiotic Centre and Prof Paul Ross of Teagasc, Moorepark, have recently turned to "bioengineering" as a way to learn more about lantibiotics and also to develop more powerful forms of these bacteriocins.

They started with a known lantibiotic and then used bioengineering to produce thousands of similar, but slightly different, forms, each one with a marginally changed DNA genetic blueprint.

The method relies on a well-known DNA- copying technique known as polymerase chain reaction (PCR), but in this case they employ a less efficient PCR method. This "error prone PCR" produces many close but not exact copies of the target DNA.

This recombination work, carried out mainly by PhD student Des Field, delivered 8,000 separate variants and each of these was screened for its antibacterial properties, Cotter says.

"We now have peptides with better activity against MRSA," he says, with four of particular interest given they all may have commercial potential. These are being tested as bacteriocins, but are now also going through additional modification using the error-prone PCR approach.

"We are trying to take the existing changes and make more changes on top of that to make them more effective," Cotter explains.

There would be an immediate market for any new substance capable to reducing the threat posed by antibiotic resistant organisms such as MRSA and other difficult to control infectious agents.

Many of the organisms of interest are food borne and so the use of a substance naturally found in a food product would have particular advantages, not least the fact that we already know these substances are not harmful to us.

• The Pierce Prize was first awarded by Oxoid Ltd in 1984 and commemorates the life and work of the late WH Pierce, who was a former chief bacteriologist for the company.