Researchers at the University of Bath in the UK have discovered a compound that can both inhibit MRSA superbacteria and make it more vulnerable to antibiotic in laboratory experiments. Antibiotic resistance poses a major threat to human health around the world, and Staphylococcus aureus has become one of the most notorious multidrug-resistant pathogens.
Under the leadership of University of Bath Maisem Laabei and Ian Blagbrough, scientists have discovered a compound that not only inhibits methicillin-resistant Staphylococcus aureus (MRSA) superbacteria, but also makes it more vulnerable to antibiotics.
Staphylococcus aureus is a bacteria found on people's skin. Staphylococcus are usually harmless, but they can cause severe infections and can lead to sepsis or death. Methicillin-resistant Staphylococcus aureus (MRSA) is a cause of staphylococcus infection with , and it is difficult to treat because it is resistant to certain antibiotics.
This novel compound - an polyamine - seems to destroy Staphylococcus aureus by destroying the pathogen's cell membrane , a bacteria that causes fatal MRSA infection.
This compound was tested in vitro for 10 different antibiotic-resistant S. aureus strains. Some strains tested are known to be resistant to vancomycin - vancomycin is the "last line" drug for patients with MRSA infection. This new compound is perfectly effective for all strains and prevents bacteria from growing.
In addition to directly destroying Staphylococcus aureus, the study also showed that the compound can restore the sensitivity of multidrug-resistant strains to three important antibiotics ( daptomycin , oxazoline and vancomycin). This could mean that antibiotics that have lost their effectiveness due to decades of overuse, over time, humans may regain the ability to control severe infections. "We are not entirely sure why these synergies occur between this compound and antibiotics, but we would like to explore this problem further," said Dr. Laabei, a researcher at the Department of Living Science at the University of Bath. "We are not completely sure why these synergies occur between this compound and antibiotics, but we would like to explore this problem further." The fragility of the pathogen
polyamines are naturally occurring compounds found in most organisms and interact with negatively charged molecules such as DNA, RNA and protein . Until a decade ago, they were considered necessary for all life, but scientists now know that they are neither present nor toxic to them in Staphylococcus aureus. Since this discovery, scientists have been trying to use the pathogen's abnormal vulnerability to polyamines to inhibit bacterial growth.
Now Dr. Laabei and his colleagues have discovered that a modified polyamine (named AHA-1394) is far more effective than the most active natural polyamine in destroying antibiotic-resistant strains of Staphylococcus aureus. Transmission electron microscope image of MRSA clinical isolate with
300,000 times enlarged. Source: Maisem Laabei/University of Bath
Dr. Laabei said in an explanation. "Using our new compound, when it is used at a concentration of more than 128 times lower than the concentration required to destroy pathogens when we use natural polyamines, the pathogen is destroyed -- meaning growth is inhibited.
" This is important because the drug with the lowest inhibitory concentration may be the more effective antibacterial agent , and is safer for patients." While further research is needed, Dr. Laabei believes that the new compound "can be clinically important as a new therapeutic option."
he said, "preliminary studies show that the compound is non-toxic to the human body, which is of course crucial." In the next study we are seeking funding, we hope to focus on the precise mechanisms of this compound used to inhibit Staphylococcus aureus. We believe this compound attacks the bacterial membrane of Staphylococcus aureus, causing the membrane to become permeable and thus let the bacteria die. "
The compound is also tested against biofilms, which are thin and difficult to handle microbial layers growing on hard surfaces (such as plaque on teeth or stubborn films on catheters) that can cause severe infection.The results in this regard are also promising, which prevent the formation of new biofilms, although there is no damage to the formed biofilms.
Antibiotic resistance
Antibiotic resistance (or antibiotic resistance-AMR) poses a major threat to human health around the world, and Staphylococcus aureus has become one of the most notorious multidrug-resistant pathogens.
A recent study reviewed the health effects of AMR in 2019 and found that the pathogen was associated with 1 million deaths worldwide because the infection did not respond to antibiotics.
Staphylococcus aureus is found in 30% of the population and lives in people's nasal cavity and skin, and in most cases it does not cause infection. Until recently, MRSA infection was considered a hospital problem, with the affected people mainly those whose immune systems are already damaged. However, over the past 20 years, community-wide infections have been rising due to complex and only partially understood reasons, even among other healthy people, which has brought a sense of urgency to seek new ways to solve this problem.
"New treatments are urgently needed to treat infections," said Dr. Laabei.
