Researchers transform old drug into new fighter against antibiotic resistance

Scientistshave been losing theirupper hand in the antibiotic arms race against infectious disease for years.But a group of researchers at McMaster University claim they've discovered anew fighter against drug resistance in a surprising source.

An existinganti-fungaldrug pentamidine commonly used to treat pneumoniaand HIV is believed to offer a solution against these superbugs, when taken in combination with antibiotics.

"What we're talking about now is a molecule that's already a drug that can make a number of antibiotics, that are formerly not useful for the treatment of gram-negative bacteria, capable of treating this class of organisms," said Eric Brown, lead researcher on the trial and a professor of biochemistry and biomedical science at McMaster's Mchael G. DeGroote School of Medicine.

Misuseimpacts resistance, WHO says

Antibiotic resistance happens when bacteria change and become able to withstand the antibiotics used to treat the infections they cause.

• WHO's 'priority pathogens' list highlights urgent need for new drugs

Overuse and misuseof antibiotics increase the development of resistant bacteria, the World Health Organization says.

Targeting antibiotic resistant bacteria

A cluster of bacteria, called gram-negative bacteria developedan ingenious system to protect themselves against any molecule that might kill them.

• Ontario scientist thinks old drugs could become our new antibiotics

They have two cellular walls, making it harder for drugs to penetrate the double exterior membranes, and are equipped with pumps and other tools to reject drug molecules, Brown explained.

This drug-resistant bacteria blocks out all antibiotics, including last resort drugs.

'This is an existing drug'

Fouryearsago,Brown took an alternative approach, by focusing on dismantling thisbacteria's most challenging aspect.

"Our strategy was to target that outer membrane and find ways to disrupt it," he told CBC News.

What we're talking about now is a molecule that's already a drug that can make a number of antibiotics, that are formerly not useful for the treatment of gram-negative bacteria, capable of treating this class of organisms.- Eric Brown, microbiologist

Modern technology enabled these researchers to screen more than500,000 compounds from nearly 2,000 off-patent drugs, giving them the tools to uncover the pentamidine compound and test its effectiveness when combined with antibioticsin mice.

"It's pretty interesting to me that this is an existing drug," Brown said.

"Most of the stuff that goes on in my lab is pretty far from the clinic, in terms of the discoveries we make and the kind of science that we do. Butthe fact that a known drug can do this so effectively I think is pretty exciting in terms of the prospect to move this more quickly into the clinic."

The shortcomings of pentamidine

But Brown explained this isn't a catch-all solution.

Research uncovered that thepentamidinecocktail wasonly effective in Acinetobacter baumanniiand enterobacteriaceae bacteria.

It didn't have the same success inPseudomonasaeruginosabecause "the outer membrane is somehow subtly different."

"The composition of these membranes isn't identical and we think that might be at the root of the differences that we saw," he added.

Pentamidine also has some "shortcomings with long-term use."

"There are some known toxicities for pentamidine," he stated.

These side-effectsinclude liver and kidney damage, which are typically seen in patients who take the drug for three weeks or more.

Brown says he hopes to address this in future research.

"We wonder if we can come up with a better pentamidine, with subtle changes to the structure of that compound," he said.