Historic Discovery Reveals New Weapon Against Drug-Resistant Bacteria

The world urgently needs new antibiotics. In 2019 alone, antibiotic-resistant bacteria killed more than 4.5 million people worldwide. The bacteria that cause these infections evolve constantly, becoming resistant to treatments faster than scientists can find replacements.

Finding effective new medicines, especially against hard-to-treat Gram-negative bacteria, is critical. Now, a recent discovery might offer hope, thanks to researchers at McMaster University who uncovered a promising new antibiotic named lariocidin.

Antibiotics changed medicine by helping fight bacterial infections. But over time, bacteria adapted, developing ways to resist even the strongest antibiotics. This problem, called antimicrobial resistance (AMR), makes infections harder to treat, leading to longer hospital stays, higher medical costs, and increased death rates.

Antibiotic resistance is now considered one of the biggest health threats globally. The World Health Organization (WHO) classifies some resistant bacteria as "critical threats," requiring immediate attention.

“Our old drugs are becoming less and less effective as bacteria become more and more resistant to them," explained Gerry Wright, a professor in biochemistry and biomedical sciences. Wright leads the McMaster team behind this new discovery. He noted, "About 4.5 million people die every year due to antibiotic-resistant infections, and it's only getting worse."

Traditionally, antibiotics came from naturally produced peptides—small chains of amino acids. Most medically useful peptide antibiotics are made by bacteria and fungi through specialized enzyme systems. These peptides, such as penicillin and vancomycin, effectively treat infections by targeting specific bacterial functions.

A newer category, called ribosomally synthesized and post-translationally modified peptides (RiPPs), has attracted interest lately. These peptides start as simple proteins and are transformed by enzymes into active antibiotics.

A fascinating subgroup, called lasso peptides, has a unique structure resembling a lasso: the peptide chain loops into itself, forming a stable knot-like shape. Because of this tight structure, lasso peptides are tough and long-lasting.

While some known lasso peptides, like lassomycin, stop bacteria from growing by targeting enzymes or interfering with RNA, none were previously known to target the bacterial ribosome—the protein-making machinery itself.

Until now.

Gerry Wright and his research team discovered lariocidin by examining soil samples from a backyard in Hamilton, Canada. Their careful method allowed slow-growing bacteria, often overlooked, to thrive in the lab over one year. Among them, they identified a type of bacteria producing a powerful compound effective against resistant pathogens.

"When we figured out how this new molecule kills other bacteria, it was a breakthrough moment," said Manoj Jangra, a postdoctoral fellow involved in the study.

Lariocidin works differently than any antibiotic currently available. Unlike existing medicines that typically target bacterial enzymes or known ribosomal sites, lariocidin binds to a completely new site on the ribosome. The ribosome is vital because it translates genetic instructions into proteins needed for bacterial growth. By interrupting this critical process, lariocidin effectively halts bacterial survival.

"This is a new molecule with a new mode of action," Wright emphasized. "It's a big leap forward for us."

Bacteria resist antibiotics through several mechanisms. One common method involves altering or blocking known antibiotic-binding sites on the ribosome. Since lariocidin attaches to a previously unknown site, bacteria have no existing defenses against it. This makes lariocidin especially promising against resistant strains that traditional antibiotics cannot defeat.

In tests, lariocidin successfully eliminated drug-resistant Gram-negative bacteria, which are especially dangerous due to their tougher outer membranes. Furthermore, this peptide proved safe for human cells and effective in animal models, two critical hurdles any new antibiotic must pass.

Wright’s team found lariocidin meets key criteria for a successful antibiotic candidate:

These features give lariocidin substantial potential for clinical use.

Despite this exciting discovery, bringing lariocidin to pharmacies remains a complex challenge. Although bacteria naturally produce antibiotics, they do so for their own survival—not human medical needs. Producing enough antibiotic for widespread medical use will take significant time and resources.

"The initial discovery—the big a-ha! moment—was astounding for us," Wright shared. "But now the real hard work begins. We're now working on ripping this molecule apart and putting it back together again to make it a better drug candidate."

Currently, Wright’s team is modifying lariocidin to improve its strength, safety, and stability. The ultimate goal is developing an antibiotic powerful enough to combat today's toughest bacterial infections.

New antibiotics matter because bacteria are evolving rapidly. If antibiotics lose effectiveness entirely, common illnesses and routine surgeries could become deadly. According to experts, failure to find new antibiotics could return us to a pre-antibiotic era when even minor infections posed serious risks.

Today’s antibiotics mostly target the same sites on bacterial cells. Continued overuse allows bacteria to develop resistance faster. To slow resistance, scientists urgently need antibiotics that strike new targets with different methods. Lariocidin’s novel approach—disrupting bacterial protein synthesis through a unique binding site—could help break the cycle of resistance.

This discovery marks the first potential new class of antibiotics in nearly 30 years. It shows promise not just for treating existing resistant infections but also for staying ahead in the ongoing arms race against bacterial evolution.

Wright believes the discovery offers fresh hope in a field desperate for solutions. "Our goal isn't just another antibiotic," he concluded. "It's an antibiotic that bacteria haven’t seen yet—one they can't resist."

Study research findings were published in the journal Nature.

Note: The article above provided above by The Brighter Side of News.

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