Innovative drug destroys drug-resistant superbugs

In laboratory tests, the new compound eradicates 10 strains of antibiotic-resistant MRSA. (CREDIT: Creative Commons)

A compound that inhibits the superbug MRSA and makes it more vulnerable to antibiotics has been discovered by scientists at the University of Bath in the UK led by Dr Maysem Laabey and Dr Ian Blagbrough.

The new compound, a polyamine, appears to kill Staphylococcus aureus, the bacterium that causes (among other things) the deadly methicillin-resistant Staphylococcus aureus (MRSA) infection, by disrupting the pathogen’s cell membrane.

The compound has been tested in vitro against 10 different antibiotic-resistant strains of S. aureus, including those known to be resistant to vancomycin, the latest drug of choice in patients battling MRSA infection. The compound was completely effective against all strains, resulting in the cessation of further bacterial growth.

The study shows that, in addition to directly killing S. aureus, this compound is able to restore the sensitivity of multidrug-resistant bacterial strains to three important antibiotics (daptomycin, oxacillin and vancomycin). This could mean that antibiotics rendered ineffective by decades of overuse may eventually regain their ability to control serious infections.

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“We’re not entirely sure why there is such a synergy between the compound and antibiotics, but we’re keen to explore it further,” said Dr. Laabey, a researcher at the Department of Life Sciences in Bath.

pathogen vulnerability

Polyamines are natural compounds found in most living organisms. Ten years ago, they were thought to be essential to all life, but scientists now know that they are absent from S. aureus and are toxic to it. After this discovery was made, researchers tried to exploit the pathogen’s unusual vulnerability to polyamines to suppress bacterial growth.

Now Dr. Laabey and his colleagues have found that a modified polyamine (named AHA-1394) is much more effective at killing antibiotic-resistant strains of Staphylococcus aureus than even the most active natural polyamine.

Transmission electron microscope image of a clinical MRSA isolate at 300,000x magnification. (CREDIT: Maisem Laabei/University of Bath)

Explaining, Dr. Laabey said: “With our new compound, the pathogen is killed – that is, growth is inhibited – when it is used at a concentration that is more than 128 times lower than that required to kill the pathogen when we use natural polyamine.

“This is important because drugs with the lowest minimum inhibitory concentration are likely to be more effective antimicrobial agents and safer for the patient.”

While further research is needed, Dr. Laabey believes the new compound “could be important in the clinical setting as a new treatment option.”

He said: “Preliminary studies show that the compound is not toxic to humans, which is of course important. In our next study, for which we are seeking funding, we hope to focus on the exact mechanisms used by the compound to inhibit S. aureus. We believe that the compound attacks the S. aureus membrane, causing the membrane to become permeable, resulting in the death of the bacteria.”

The compound has also been tested against biofilm, a thin, hard-to-treat layer of microorganisms that grows on hard surfaces (visible, for example, as plaque on teeth or a persistent film on urinary catheters) and can lead to serious infection.

The results here were also promising: the compound prevented the formation of a new biofilm, but did not destroy the existing biofilm.

Antibiotic resistance

Antibiotic resistance (or antimicrobial resistance – AMR) is a major threat to human health worldwide, and S. aureus has become one of the most infamous multidrug-resistant pathogens.

A recent 2019 health impact study of AMR found that this pathogen was associated with one million deaths worldwide from infections refractory to antibiotics.

S. aureus is found in 30% of the population, living in the nasal passages of people and on the skin, and for the most part does not cause infection. Until recently, MRSA infection was seen as a hospital problem, and those affected were mostly people with already weakened immune systems.

However, over the past 20 years, for complex and only partially understood reasons, there has been a community-wide surge in incidence even among healthy people, making the search for new ways to solve this problem urgent.

“New therapies are urgently needed to treat infections,” Dr. Laabey said.

“Antibacterial activity of novel linear polyamines against Staphylococcus aureus” published in Frontiers in Microbiology.

To learn more about science and technology, visit our New Innovations section at The bright side of the news.

Note: Materials provided by the University of Bath. Content can be edited for style and length.

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