Blood Pressure Medication Shows Promise in Fighting MRSA

A study suggests that a blood pressure medication might be effective against a widespread bacterial infection that’s tough to treat.

Researchers from the Houston Methodist Research Institute in Texas have found that Candesartan cilexetil could potentially combat methicillin-resistant Staphylococcus aureus, commonly known as MRSA, which is known for its resistance to antibiotics.

In laboratory and animal experiments, this medication disrupted the membranes of MRSA cells, impairing their function and leading to their death.

Candesartan, often referred to as CC, is inexpensive and is already used to manage high blood pressure and heart failure. If its efficacy against MRSA is validated in human studies, it could be an appealing option for treatment.

“I think CC is among the most promising agents we’ve discovered,” said Eleftherios Mylokanis, the senior author of the study.

Mylokanis, who specializes in infectious diseases, noted that MRSA is one of the most prevalent resistant bacteria he encounters.

This particular strain can lead to serious issues including skin, lung, or bloodstream infections. According to the Centers for Disease Control and Prevention, MRSA is responsible for over 70,000 severe infections and around 9,000 deaths in the U.S. annually.

Antibiotic-resistant microbes like MRSA pose an increasing threat to public health, attributed to over 1.27 million fatalities globally in 2019 alone.

Despite the urgent need, the development of new antibiotics has not kept up with the growing resistance issue. Mylokanis pointed out that the market for antibiotics isn’t lucrative, leading many companies to shy away from investing in their development.

“The market is completely upside down,” he observed. “The better an antibiotic is, the more we hesitate to use it, fearing it will foster resistance.”

He and his team are actively searching for new candidates for antimicrobial treatment.

Previously, they screened more than 80,000 compounds to find effective drugs against MRSA using infected worms. Candesartan cilexetil emerged as one of the few beneficial options.

To delve deeper, the researchers evaluated how Candesartan interacts with MRSA through simulations and advanced imaging techniques.

They also looked at the genetic material, small molecules, and lipids involved, testing the drug’s effectiveness in various combinations with existing antibiotics.

“We built our understanding gradually, piece by piece,” said Nagendran Tharmalingam, a microbiologist from Houston Methodist and the first author of the study. “We discovered that this drug causes injury to the membrane.”

The cell membrane plays a crucial role in maintaining structure and controlling what enters the cell.

Candesartan binds to the MRSA membrane, penetrating it and causing damage that ultimately results in cell death. Imaging revealed that the drug created holes in the bacteria’s membranes, allowing cell contents to leak out.

The study also indicated that Candesartan can target chronic MRSA, which can remain dormant in the body and later reactivate.

Additionally, when combined with other antibiotics, like gentamicin, Candesartan produced a more substantial effect at lower dosages than using either drug alone.

In animal models, the drug significantly lowered the bacterial load, reinforcing the potential of Candesartan against MRSA in humans.

The research team is also working on chemically modifying Candesartan to create new compounds that could be more effective and possibly have fewer side effects.

They hope to collaborate with a pharmaceutical or biotech company for further testing of Candesartan cilexetil in human trials, and they’ve reported promising initial feedback.

“Our goal is to transition this from laboratory research to clinical application,” Tharmalingam stated.

The findings of this research were published in Nature Communications.