Kiwis’ finding key to drug resistance fight

Otago scientists link gene behaviour with urgent health problem

Kiwi scientists have made a surprise genetic finding that could help combat drug resistance — an urgent health problem facing the world. University of Otago researchers were investigating how yeast — the single-celled organism behind a range of human infections — becomes drug resistant when they hit upon an unexpected understanding that may lead to new ways to overcome it.

At the centre of the breakthrough was a previously unknown piece of genetic sleight-of-hand which may enable multi-drug resistance.

“When a gene mutates and has another function, the original gene function is lost,” explained Dr Erwin Lamping, of the university’s Sir John Walsh Research Institute.

“However, another way organisms adapt is by gene duplication, where they make a second copy of the gene.”

This meant if one copy mutated and changed its function, the organism still had the original gene with its original function. “This allows organisms to adapt by using almost identical genes to develop a range of different functions or abilities.”

While studying how the yeast behind human infections such as oral and vaginal thrush became drug resistant, Lamping and his team found the organism created a protein that pumped the drug out of the yeast cell.

“We also found, by chance, that there was a very similar gene next door — an example of gene duplication,” Lamping said.

“What we discovered, which has not been found before, was that while large parts of the adjacent genes were identical, six short regions were different and had remained different for over 130 million years.”

The reason they had remained different, he said, was they were the regions that allowed the two pumps to pump different drugs.

“We carefully studied genes from seven yeast strains originating from different parts of the world and found 30 copies of the pump gene, all with the same pattern: they had large regions that were exactly the same and small regions that differed.”

This showed that the mechanism of evolution was widespread, in the entire yeast population studied.

“This repetition of almost identical genes, but with different functions, may have gone unnoticed in other organisms including humans.”

The research, supported by the Marsden Fund and just published in the journal Genetics, may help explain why cancer cells become resistant to multiple drugs, why people react differently to drugs and why some drugs do not work for some people.

It comes as another Otago researcher, biochemist Professor Iain Lamont, begins a collaborative study to uncover the genetic mutations that lead to antibiotic resistance in the superbug Pseudomonas aeruginosa.

Dr Tania Pocock, acting chief executive of the Health Research Council, which has contributed $1.15 million to Lamont’s project, said an estimated 700,000 people died worldwide each year from infection by antibiotic-resistant superbugs — and the rate could rise to 10 million unless new treatments or approaches were adopted.