The new compound that destroys the MRSA superbug

Scientists from the University of Bath led by Dr. Maisem Laabei and Dr. Ian Blagbrough have discovered a compound that both inhibits the MRSA superbug and makes it more susceptible to antibiotics.

The novel compound – a polyamine – appears to destroy Staphylococcus aureus, the bacterium that causes (among other things) deadly methicillin-resistant Staphylococcus aureus (MRSA) infections, by destroying the pathogen’s cell membrane.

The compound was tested in vitro against 10 different antibiotic-resistant strains of S. aureus, including some known to be resistant to vancomycin – the last drug of choice for patients battling MRSA infection. The compound was completely successful against all strains, resulting in no further bacterial growth.

The study shows that the compound not only destroys S. aureus directly, but can also restore the susceptibility of multidrug-resistant bacterial strains to three key antibiotics (daptomycin, oxacillin and vancomycin). This could mean that antibiotics, rendered ineffective by decades of overuse, could regain their ability to control serious infections over time.

“We’re not entirely sure why these synergies occur between the compound and antibiotics, but we want to investigate this further,” said Dr. Laabei, researcher from the Department of Live Sciences in Bath.

The susceptibility of the pathogen

Polyamines are naturally occurring compounds found in most living organisms. Until a decade ago they were considered essential to all life, but scientists now know that they are both absent from S. aureus and toxic to S. aureus. Since this discovery, researchers have tried to exploit the pathogen’s unusual susceptibility to polyamines to inhibit bacterial growth.

Now have dr. Laabei and his colleagues found that a modified polyamine (dubbed AHA-1394) is much more effective at destroying antibiotic-resistant strains of S. aureus than even the most active natural polyamine.

By way of explanation, Dr. Laabei that “when using our novel compound, the pathogen is destroyed – meaning growth is inhibited – when used at a concentration over 128 times lower than that required to destroy the pathogen when used we use a natural polyamine.”

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

Although more research is needed, Dr. Laabei said the new compound “could have important implications in a clinical setting as a new treatment option.”

He says that “preliminary research suggests that the compound is non-toxic to humans, which of course is imperative. In our next study, which we are seeking funding for, we hope to focus on the precise mechanisms used by the compound to generate S. aureus. We believe the compound attacks the membrane of S. aureus, causing the membrane to become permeable, leading to bacterial death.”

The compound has also been tested against biofilm – the thin, difficult-to-treat layer of microorganisms that grows on hard surfaces (e.g. seen as plaque on teeth or a stubborn film on urinary catheters) and can lead to serious infections. Again, the results were promising: the compound prevented the formation of a new biofilm, but did not disrupt the established biofilm.

antibiotic resistance

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

A recent study looking back at the health effects of AMR in 2019 finds that the pathogen has been linked to one million deaths worldwide resulting from infections that did not respond to antibiotics.

S. aureus occurs in 30% of the population, lives in people’s nasal passages and on the skin, and most of the time does not cause infection. Until recently, MRSA infection was considered a hospital problem, mostly affecting people with already weakened immune systems. However, over the past 20 years, for complex and only partially understood reasons, there has been an increase in community-wide infections, even among otherwise healthy individuals, urging the search for new ways to solve the problem.

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

The study was published in frontiers in microbiology.