How antibiotics could fight superbugs: Canadian scientists make key discovery

Gerry Wright, left, and Manoj Jangra are part of the research team that discovered a new class of antibiotics called lariocidin in Hamilton, Ont. (McMaster University) (Georgia Kirkos)

For the first time in decades, researchers have found a new class of antibiotics that could effectively fight superbugs, which are some of the planet’s most drug-resistant bacteria.

The discovery of antibiotic-producing bacteria in soil from a backyard was the first step in what could be the development of new antimicrobial medicines with the potential to cure life-threatening conditions, from pneumonia to urinary tract infections, according to researchers from McMaster University in Hamilton, Ont., who conducted a study published in the science journal Nature on Wednesday.

They found a strain of bacteria, called Paenibacillus, produced a new class of antibiotics, a chemical called lariocidin. Antibiotics are medicines that treat or prevent bacterial infections by killing bacteria or stopping them from reproducing.

Lariocidin is effective against multidrug-resistant bacteria that pose a significant threat to society, Manoj Jangra, a postdoctoral fellow at the McMaster University lab that made the discovery, said in a video interview with CTVNews.ca on Tuesday.

The findings come after the World Health Organization in 2023 flagged antimicrobial resistance as one of the top global public threats.

Gerry Wright, lead researcher for the Nature study, says the problem is getting worse. Existing drugs have become less effective as bacteria mutate and become more resistant to them, he adds.

What’s more, antibiotic resistance killed more than 4.5 million people in 2019, according to the Nature study.

“We’re in a pretty significant crisis of resistance to our existing antibiotics in the world today,” said Wright, a professor in biochemistry and biomedical sciences at McMaster University, in a video interview with CTVNews.ca on Monday. “And so we need candidates for new antibiotics that are not susceptible to this resistance.”

The scientists found a solution in the backyard soil sample in Hamilton, Ont. Wright said lariocidin is promising as a potential drug with “remarkable properties” because it attacks bacteria in a way that prevents them from growing and surviving.

McMaster researchers also worked with peers from the University of Illinois in Chicago with expertise on the ribosome, the unit inside the bacterial cell responsible for the production of proteins, and the target of lariocidin.

Lariocidin, also known as a lasso peptide, contains a structure that’s “very unique” from other antibiotics, allowing it to bind to the ribosome where it stops the bacteria from making proteins, which is essential for cells to function, and causes cells to die, Wright said.

To add to that, they found that the lariocidin antibiotic is not toxic to human cells and is effective when tested in mice.

Still, Wright said scientists need to eventually test the antibiotic for toxicity in humans.

The breakthrough

The team made its breakthrough after a McMaster lab manager collected a backyard soil sample in 2019 and a postdoctoral fellow isolated the bacteria from it around a year later.

Then in 2021, Jangra joined the McMaster lab.

Their aha-moment arrived around March 2022: Jangra discovered that one of the bacteria, Paenibacillus, produced lariocidin, the new substance that killed other bacteria, including those typically resistant to antibiotics, and the team figured out how that happened.

“I discovered this new antibiotic from a (soil-dwelling) bacterium — this was exciting for us,” said Jangra, whose expertise is in isolating antibiotics from microbes. Jangra has been doing antibiotics research since 2014. “So we collect … soil samples from across different places, and then we isolate microbes (bacteria and fungi) from the soil samples ... and then you can test these (microbes) if they are producing some antibacterial substances.”

They did experiments and found that lariocidin would attack bacteria and prevent proteins from forming, which stopped their growth and ultimately killed them.

Jangra said the team infected the mice with an extremely drug resistant and deadly pathogen called Acinetobacter baumannii, which has gained resistance to most antibiotics worldwide.

The pathogen can cause pneumonia, urinary tract infections, as well as infections in the bloodstream and in wounds, and if the bacteria spreads, it can cause septic shock and organ failure, Jangra said. Those who are immunocompromised are most at risk of complications and death if they contract this pathogen, usually found in hospitals.

The mice treated with lariocidin survived, but the untreated animals died within 24 to 28 hours, he said.

The researchers hope that they can target these superbugs, or pathogens that have acquired resistance to most or all antibiotics, with the newly discovered lariocidin antibiotic in humans some day.

What’s next

The McMaster University lab is now working on finding ways to modify bacteria-produced lariocidin and generate larger amounts of it, so it can be developed into potentially stronger medicine and tested one day in humans, such as for skin, lung and bloodstream infections.

“There’s a long way before this new antibiotic can be administered to patients,” Jangra said, noting it could take at least a decade.

“So this compound is working effectively in an animal model of infection, but before it can be successfully reached to patients, we need to have several tests, like we need to test if it has any side effect or what dose we need to give. So then we have to go through a pre-clinical stage and then the clinical trials.”