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Break down walls - and heal

How to overcome bacterial resistance to antibiotics? Weizmann Institute of Science scientists propose to treat antibiotic-resistant infections by breaking the protective walls of bacterial colonies known as "biofilm"


Calcium carbonate walls that protect a bacterial colony. Illustration: Weizmann Institute
Calcium carbonate walls that protect a bacterial colony. Illustration: Weizmann Institute

Breaking concrete walls - this is not exactly a recommendation we would expect to hear from a family doctor, but Weizmann Institute of Science scientists believe that this is one way to overcome bacterial resistance to antibiotics. In a new study thatRecently published They suggest treating antibiotic-resistant infections by breaking down the protective walls that build bacterial colonies called "biofilms."

In the past, the group of Dr Ilana Kolodkin-Gal, from the Department of Molecular Genetics, that bacteria organized in colonies build around them A calcium carbonate fortress, a hard mineral from which pearls are made, and is also used in the construction industry to produce concrete. In the new study, led by Dr. Alona Keren-Paz, the scientists wanted to reveal the structure of this fortress and its functions, and find out how to destroy it. Dr. Vlad Brumfield from the Department of Chemical Research Infrastructures, and Dr. Yara Oppenheimer-Shanan, a former post-doctoral researcher in Dr. Kolodkin-Gal's laboratory, also participated in the study.

With the help of a new method they developed for creating three-dimensional images using high-resolution x-rays, the scientists discovered that the use of the word "fortress" is not just a metaphor: the calcium carbonate organized itself into a neat crystalline structure, with walls and a ceiling. "Apparently, the walls allow the bacterial colony to build itself up, and the ceiling protects it from external factors," explains Dr. Kolodkin-Gal. The "fortress" makes up about 20% of the dry weight of the biofilm, similar to bones in the human body. Also, in both cases these are hard calcium compounds (calcium phosphate when it comes to bone), which are held by a texture of protein fibers.

From the right: Dr. Ilana Kolodkin-Gal and Dr. Alona Keren-Paz. hit a wall Photo: Weizmann Institute Spokesperson
From the right: Dr. Ilana Kolodkin-Gal and Dr. Alona Keren-Paz. hit a wall Photo: Weizmann Institute Spokesperson

Later, the scientists showed that the calcium carbonate in the biofilm prevents the fluttering of fluorescent dye molecules, and also the fluttering of antibiotics. This fact may explain why bacterial colonies organized in biofilm show resistance to antibiotics that is on average 1,000 times higher than that of bacteria living outside the colonies. Moreover, the scientists showed that the bacteria themselves are not resistant at all: the antibiotics killed them as soon as they were pulled out of the protective shell of the biofilm. In other words, the calcium carbonate created a physical barrier that protected them from the drug. "It's like throwing antibiotics at a wall - it just won't penetrate," explains Dr. Kolodkin-Gal.

It is now known that a biofilm of bacteria forms on valves implanted in the heart, and on other implants in the body. Also, scientists hypothesize that biofilm development causes complications in many chronic diseases, such as diabetes, tuberculosis, arthritis, and cystic fibrosis. The institute's scientists examined tissue samples from patients, and discovered that a biofilm was indeed formed in tissues affected by a number of diseases. The researchers also discovered that the bacteria built the protective walls of the biofilm from calcium and carbon dioxide with the help of an enzyme called urease. As part of its activity, this enzyme helps to build calcium carbonate by reducing the acidity of the environment. Therefore, when the scientists introduced a molecule that blocks the enzyme into a laboratory vessel, no calcium carbonate was formed. "It is possible that in the future it will be possible to effectively treat many resistant infections, if only we succeed in destroying the walls of the biofilm to allow the medicine to penetrate," says Dr. Kolodkin-Gal.

And in the meantime, in the near future, the findings may help diagnose patients and match them with a more correct treatment with the help of a test that will identify the biofilm in the body, and make it possible to know if antibiotics can defeat the infection.

Close-up of the calcium carbonate walls
Close-up of the calcium carbonate walls

The new construction workers

Understanding how calcium carbonate is formed in a biofilm may also lead to the opposite goal: instead of destroying it, use it for construction - for example, to develop concrete that repairs itself. Dr. Kolodkin-Gal, together with Dr. Keren-Paz and a British architect and scientists, recently examined the feasibility of this proposal. their article Appeared in the scientific journalMicrobial Biotechnology, in a special issue dedicated to the contribution of bacterial biotechnology to sustainable development.

In this article, the scientists proposed to inject bacteria into the concrete, in order to repair cracks or other damages caused by drift or displacement of the ground. According to the proposal, the cracks in the concrete will be filled with calcium carbonate, which will produce a biofilm of bacteria. The use of carbon dioxide in the calcium production process will also reduce the amount of greenhouse gas in the atmosphere.

In the video: XNUMXD simulation of the barrier protecting a bacterial colony. Photographed using high-resolution X-ray tomography.


for the scientific article

More of the topic in Hayadan:

A bacterial colony organized in a biofilm contains about 1,000,000,000 bacteria on average.


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