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A new type of drug may provide a way to treat multidrug-resistant bacteria, according to a new study Natural relationships. Instead of directly targeting the bacteria, the drug blocks key toxins involved in the infection process. This both reduces inflammation and makes the bacteria more susceptible to antibiotics.
Antibiotics are useful in the fight against bacterial diseases, but bacteria are becoming increasingly resistant. When antibiotics were first introduced, it took an average of 11 years for bacteria to develop resistance, but today this figure has dropped to 2-3 years. “The situation is very serious,” said Ekaterina Osmekina, a postdoctoral researcher at Aalto University. “Many common bacterial infections are becoming resistant, and new antibiotics are not being developed fast enough to keep pace.”
In the year In 2019, 1.27 million deaths were directly attributable to antimicrobial resistance, and this number is expected to increase to 10 million per year by 2050. “We urgently need new tools to combat these resistant infections,” Osmekina said. Despite this, no new antibiotics have been approved in decades and only six currently under development can overcome resistance, only two of which target highly resistant bacteria.
A different approach is to directly target toxins and biofilms that cause pathogens to establish infection and inflammation, which are collectively called virions. These virulence factors include small molecules that bacteria use to communicate and large molecules that are part of the protective membrane. A drug that binds to these molecules can interfere with the processes necessary for bacteria.
An international team led by researchers at Aalto searched for drugs that could do just that. After screening a library to identify molecules that interact with virulence factors but do not affect bacterial growth, they found a good candidate. “Because the drug disarms the pathogen rather than killing it or stopping its growth, our approach creates a very weak selection pressure for resistant bacteria to develop,” said doctoral student Christopher Jonkergow, who led the study.
The team tested the drug against pathogenic bacteria Pseudomonas aeruginosa and Acinetobacter baumannii, which are on the World Health Organization’s priority list. The treatment involves sequestering toxins released by pathogens, disrupting their ability to communicate and forming protective biofilms, as described in this short video:
While these tests show that the drug can effectively disarm these pathogens, the researchers want to know if it can make them more vulnerable. The addition of antibiotic therapy with the new drug made the antibiotic less effective. Most importantly, when the team treated the bacteria with a combination of antibiotics and the new drug for two weeks, the bacteria became resistant to the antibiotics, even though they quickly became resistant when exposed to antibiotics alone.
This suggests that the new drug can be used to maintain the effectiveness of antibiotics.
“The medicine comes into contact with the part of the outer membrane of bacteria, which is a strong barrier against antibiotics. The medicine loosens the membrane and makes it more penetrating. This means that it is easier for the antibiotics to enter the bacteria and kill them,” explained Osmekina.
After showing that the drug was effective against bacterial pathogens, the next step was to determine whether it could actually provide protection. To test that, human lung cells were exposed to toxins that cause inflammation and cellular damage. The drug directly filters out toxins and protects against inflammation and cellular damage. The researchers found similar protective effects when mice were exposed to the poison.
While much work needs to be done before clinical trials can be conducted, these findings open the door to a new alternative to antibiotics that could break the cycle of antibiotic discovery and resistance. This treatment and others may give us the boost we need to keep ahead in the never-ending arms race against bacterial resistance.
Christopher Jonkergow et al., Reprogramming host-guest chemistry to control virulence and destroy biofilms of multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii; Natural relationships (2023) DOI: 10.1038/s41467-023-37749-6