Scientists have found a substance in garlic which could be used to fight the dreaded lung disease cystic fibrosis. The substance, ajoene, breaks down the bacterial communication system, making it easier to kill the bacteria. Ajoene has already proven itself effective against bacteria involved in cystic fibrosis in trial mice. (Photo: Coulourbox)

Garlic – the new weapon against cystic fibrosis

New research shows that garlic has a substance that could be the drug industry’s new weapon against serious complications of the dreaded lung disease cystic fibrosis.

Danish scientists have discovered a natural garlic compound, ajoene, which can prevent bacteria communicating and collaborating with each other – making it easier to kill the bacteria.

The research shows that ajoene is especially effective in fighting the bacteria Pseudomonas aeruginosa, which gives chronic infections in patients suffering from cystic fibrosis.

The findings have been published in the scientific journal Antimicrobial Agents and Chemotherapy.

“We have found a substance which effectively blocks the bacteria’s ability to communicate with each other,” says PhD student Tim Holm Jakobsen of the Department of International Health, Immunology and Microbiology at the University of Copenhagen.

We have found a substance which effectively blocks the bacteria’s ability to communicate with each other.

Tim Holm Jakobsen

“Ajoene also prevents the bacteria secreting rhamnolipid, a substance that destroys the body’s white blood cells – which are designed to kill bacteria and prevent infections.”

Together with his research group, headed by Professor Michael Givskov, Jakobsen has studied the antimicrobial properties of garlic for six years and is responsible for the new research result, expected to be of great benefit to patients with cystic fibrosis.

Most serious complication is bacteria in the lungs

Cystic fibrosis is an incurable hereditary disease that slowly destroys the lungs, making breathing difficult for patients. In Denmark, 12-15 children are born with the disease every year.

In patients with cystic fibrosis, some of the molecule pumps in the lung tissue and elsewhere no longer function as they should.

Ajoene also prevents the bacteria secreting rhamnolipid, a substance that destroys the body’s white blood cells – which are designed to kill bacteria and prevent infections.

Tim Holm Jakobsen

This causes a build-up of a mucous layer in the lungs. As this layer is rich in nutrients and oxygen, it is an ideal place for bacteria to flourish.

This accumulation of bacteria in the lungs destroys the lung tissue over a long period and leads to cystic fibrosis patients dying from a lack of oxygen. Few patients with the disease live longer than 45 years.

For cystic fibrosis patients, one of the most dreaded bacteria is Pseudomonas aeruginosa, which often finds its way into their lungs and makes its home there.

“Eighty percent of all cystic fibrosis patients are infected by P. aeruginosa,” says Jakobsen. “After an infection, things start to look very bad. The P. aeruginosa bacteria develop quite quickly into a chronic infection, and treating this is extremely difficult. We also don’t want the bacteria to become resistant – which is often a consequence of the very intensive and comprehensive use of antibiotics during treatment.”

Bacteria communicate with each other

Ajoene alone blocked quorum sensing and the release of rhamnolipid to such a degree that the immune defence system gained enough strength to fight the normally very stubborn chronic infection without problems.

Tim Holm Jakobsen

In chronic infections in the body, bacteria form a mucous layer, called a biofilm, which not only boosts their resistance to antibiotic drugs by up to 1,000 times, but also means that they start to communicate with each other.

This communication occurs using a system known as quorum sensing. The bacteria in the biofilm combine together as a single bacterial unit, directing their attack on one place in the body for maximum impact.

It is also in the biofilm that the bacteria form substances such as rhamnolipid, which breaks down white blood cells, effectively destroying the body’s immune defences.

“If you want to fight chronic infections in the lungs, you must look at potential ways of destroying the quorum sensing function and thus the bacterial communications,” says the researcher. “In this way you can hinder the rhamnolipid attacks and strengthen the immune defences. At the same time you can hamper the bacteria without killing them, thus minimising the risk that the bacteria become resistant.”

Garlic compound may be the key

In their search for substances with the right properties, Jakobsen and colleagues studied numerous possibilities, including the garlic compound ajoene, which they believe has great potential in this application.

Ajoene does not kill bacteria directly, but it inhibits virulence genes controlled by quorum sensing. This disruption prevents the bacteria from coordinating their attacks on the body.

In laboratory trials with a biofilm comprising P. aeruginosa bacteria, the research group showed that that ajoene in combination with an antibiotic drug kills more than 90 percent of the bacteria.

Ordinary antibiotic drugs alone have no effect on the biofilm. But when a biofilm is subjected to ajoene, some of the protective structure of the biofilm disappears, giving the antibiotics easier access to the bacteria.

Trials with mice were also promising. Scientists injected P. aeruginosa into one lung of 171 mice. Then the mice were injected with ajoene in the neck. After three days, the number of bacteria in the lungs of the mice given ajoene had fallen to 1/500th of the bacteria in the control mice.

“Our mice trial showed that ajoene has an enormous effect on the biofilm in the lungs,” says Jakobsen. “Ajoene alone blocked quorum sensing and the release of rhamnolipid to such a degree that the immune defence system gained enough strength to fight the normally very stubborn chronic infection without problems.”

Used with antibiotics

The promising trials with ajoene indicate that patients with cystic fibrosis will have a potent weapon in the future in their battle against the disease.

Jakobsen believes that ajoene will be used in combination with ordinary antibiotics to win the battle against the infection that so far has killed cystic fibrosis patients. He also sees ajoene being used against other forms of chronic infection.

If a drug manufacturer chooses to develop ajoene, a product could be released on the market in about ten years, Jakobsen predicts.

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Read this article in Danish at videnskab.dk

Translated by: Michael de Laine

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