A possible cure for bacteria resistant to multiple drugs

A new class of drug could provide a way to treat multidrug-resistant bacteria, according to a study published in the journal Nature Communications. Rather than targeting bacteria directly, the drug blocks key toxins involved in the infection process. This reduces inflammation and makes bacteria more susceptible to antibiotics.

Antibiotics have been invaluable in fighting bacterial infections, but bacteria are becoming more and more resistant to them. In the early days of antibiotics, bacteria took an average of about 11 years to become resistant, but that number is down to 2-3 years today. “The situation is dire,” says Ekaterina Osmkhina, a postdoctoral researcher at Aalto University. “Many common bacterial infections are becoming resistant, and new antibiotics are not being developed fast enough to keep up.”

In 2019, it recorded 1.27 million deaths directly attributed for antimicrobial resistance, and this number is expected to rise to 10 million annually in 2050. “We urgently need new tools to tackle these resistant infections,” says Osmekhina. Despite this, no new antibiotics have been approved in decades, and they still exist Only six are currently in development that may avoid resistanceOnly two of them target highly resistant bacteria.

A different approach is to directly target the toxins and biofilms that pathogens use to establish infection and cause inflammation, collectively called virulence factors. These virulence factors include the small molecules that bacteria use to communicate and the larger molecules that are part of their protective membrane. A drug that binds to these molecules can interfere with the vital processes of bacteria.

An international team led by researchers at Aalto went looking for drugs that could do just that. they I found a good candidate Post-screen the library to identify molecules that interact with virulence factors but do not affect bacterial growth. “Because the drug disarms the pathogen rather than killing it or stopping its growth, our method generates much weaker selection pressure for developing resistant bacteria,” explains Christopher Junkergo, the doctoral student who led the study.

The team tested the drug against pathogenic bacteria Pseudomonas aeruginosa and Acinetobacter baumannii, which appear high on the World Health Organization’s priority list. The treatment sequestered the toxins secreted by the pathogens and disrupted their ability to communicate, thus reducing the formation of protective biofilms as shown in this short video:

While these trials showed that the drug could effectively neutralize these pathogens, the researchers also wanted to see if it could make them more vulnerable. Supplementing antibiotic treatment with the new drug made the antibiotic effective at a lower dose. But more importantly, when the team treated the bacteria with a combination of antibiotics and the new drug for two weeks, the bacteria did not develop antibiotic resistance, although they quickly became resistant when exposed to antibiotics alone.

This suggests that the new drug could be used to maintain the effectiveness of our remaining antibiotics.

“The drug interacts with a portion of the bacteria’s outer membrane, which is a strong barrier against antibiotics. The drug loosens the membrane and makes it more permeable. This means that it is easier for the antibiotic to get in and kill the bacteria,” Osamkhina explains.

After demonstrating that the drug was effective against bacterial pathogens, the next step was to determine if it could actually provide protection. To test this, human lung cells were exposed to toxins that cause inflammation and cellular damage. The drug directly sequesters toxins and protects them from infections and cellular damage. The researchers found similar protective results when the mice were exposed to the toxins.

While more work needs to be done before clinical trials, these findings open the door to an exciting new alternative to antibiotics, one that could break the vicious cycle of antibiotic discovery and resistance. This and other forms of treatment could provide the boost we need to get ahead in the never-ending arms race with bacterial resistance.