Hope Against Superbugs: New Class Of Antibiotics Discovered After 30 Years

Scientists have discovered a new natural molecule called lariocidin, produced by soil bacteria, that works differently than current antibiotics and can kill even resistant bacteria. It attacks the bacteria’s “protein factory” in a new way, is safe for human cells, and has worked well in animal tests. The discovery offers hope in the fight against antibiotic resistance.

Discovering new antibiotics is essential because many bacteria are becoming resistant to the drugs we use today, a phenomenon known as bacterial resistance. This means that common infections that were once easily treatable are becoming dangerous or even deadly.

Without effective antibiotics, medical procedures such as surgery, cancer treatments, and even childbirth become much riskier. New antibiotics help ensure that we can continue to fight infections and protect global public health.

Researchers at McMaster University have discovered a promising new molecule with the potential to become a powerful antibiotic against resistant bacteria, called lariocidin.

It is a special type of lasso peptide, small natural proteins with a stable and complex structure that are produced by bacteria. The big innovation here is that, unlike other antibiotics, lariocidin directly attacks the bacterial ribosome, an essential structure where bacteria produce their proteins.

Without these proteins, they cannot grow or survive. This target, the ribosome, is already known to be the site of action for several antibiotics, but lariocidin binds to it in a completely new way, never seen before, making it especially valuable against bacteria that have already developed resistance to other drugs.

The molecule was discovered in a bacterium of the genus Paenibacillus, collected in a soil sample from a common backyard in Hamilton, Canada. Scientists grew this sample for about a year, which allowed even the slowest-growing bacteria to thrive.

Soil bacteria of the genus Paenibacillus in culture

This is how they found the Paenibacillus that produced this substance with strong antibacterial activity. From there, the researchers isolated lariocidin and also a modified version of it, called lariocidin B, to study its functioning in more depth.

Laboratory tests showed that lariocidin has a powerful effect on a wide variety of bacteria, including the most difficult to treat, such as Acinetobacter baumannii, one of the main causes of resistant hospital infections. 

Acinetobacter baumannii bacteria, this is an extremely dangerous and antibiotic-resistant bacteria. It often causes serious hospital infections, especially in patients with compromised immune systems, and can affect the lungs (pneumonia), bloodstream (sepsis), wounds, urinary tract, and in rarer cases, the central nervous system (meningitis, for example, after surgery or head trauma). The most worrying thing about it is its resistance to multiple antibiotics, which makes treatment very difficult.

In addition, it has proven effective in tests with infected mice, without causing toxic effects to human cells. Another very positive point is that lariocidin is not easily affected by common bacterial resistance mechanisms, and also has a low chance of generating spontaneous resistance, which makes it a very promising candidate for the future.

This discovery is especially relevant because it has been almost 30 years since a new class of antibiotics has hit the market, and resistance to existing drugs is only growing, something that today causes the death of around 4.5 million people a year worldwide, according to the World Health Organization.

Researcher Gerry Wright, left, and postdoctoral fellow Manoj Jangra hold a 3D-printed model of lariocidin, the new antibiotic they discovered together. Credit: Georgia Kirkos, McMaster University

Lariocidin, with its unique structure and novel mode of action, could represent a significant breakthrough in the race to find effective solutions to antimicrobial resistance.

Now, the scientists face the challenge of scaling up the molecule and refining it so that it can become a viable drug for clinical use. Because it is naturally made by bacteria, this will require significant time and resources, but the team is confident that with the right tweaks, lariocidin could open a new chapter in the fight against superbugs.

READ MORE:

A broad-spectrum lasso peptide antibiotic targeting the bacterial ribosome

Manoj Jangra, Dmitrii Y. Travin, Elena V. Aleksandrova, Manpreet Kaur, Lena Darwish, Kalinka Koteva, Dorota Klepacki, Wenliang Wang, Maya Tiffany, Akosiererem Sokaribo, Brian K. Coombes, Nora Vázquez-Laslop, Yury S. Polikanov, Alexander S. Mankin, and Gerard D. Wright

Nature. 640, pages 1022–1030 (2025)

DOI: 10.1038/s41586-025-08723-7

Abstract:

Lasso peptides (biologically active molecules with a distinct structurally constrained knotted fold) are natural products that belong to the class of ribosomally synthesized and post-translationally modified peptides1,2,3. Lasso peptides act on several bacterial targets4,5, but none have been reported to inhibit the ribosome, one of the main targets of antibiotics in the bacterial cell6,7. Here we report the identification and characterization of the lasso peptide antibiotic lariocidin and its internally cyclized derivative lariocidin B, produced by Paenibacillus sp. M2, which has broad-spectrum activity against a range of bacterial pathogens. We show that lariocidins inhibit bacterial growth by binding to the ribosome and interfering with protein synthesis. Structural, genetic and biochemical data show that lariocidins bind at a unique site in the small ribosomal subunit, where they interact with the 16S ribosomal RNA and aminoacyl-tRNA, inhibiting translocation and inducing miscoding. Lariocidin is unaffected by common resistance mechanisms, has a low propensity for generating spontaneous resistance, shows no toxicity to human cells, and has potent in vivo activity in a mouse model of Acinetobacter baumannii infection. Our identification of ribosome-targeting lasso peptides uncovers new routes towards the discovery of alternative protein-synthesis inhibitors and offers a novel chemical scaffold for the development of much-needed antibacterial drugs.