Lariocidin: The Soil’s Hidden Answer to Antibiotic Resistance

Leon Wirz
Nov 3
4 min read

Published in Nature (2025), McMaster University, University of Illinois Chicago, and Rockefeller University.

Introduction

Antibiotic resistance is one of the world’s slowest-moving disasters.What started as a clinical problem has become a global health-economic threat, causing over 1.3 million deaths per year and costing health systems billions.

While bacteria continue to evolve, our medicine cabinet has barely changed in decades. Most modern antibiotics are derivatives of molecules discovered before 1980.

Now, researchers from the University of British Columbia and Rockefeller University have unearthed something truly new. A lasso-shaped peptide antibiotic called Lariocidin, produced by a soil bacterium and effective against several of the world’s most resistant pathogens.

This isn’t just another molecule. It’s a glimpse of how nature and machine learning can work together to fight the next global pandemic.

The Core Discovery

Lariocidin was discovered using a genome-mining approach: instead of screening bacteria for natural products the old-fashioned way, scientists searched bacterial DNA for hidden biosynthetic blueprints.

Deep in the genome of a forest soil bacterium, they found a cryptic gene cluster that appeared inactive under normal conditions.By transferring this gene cluster into a laboratory Streptomyces strain and using AI-based algorithms to predict structure and folding, they managed to “wake up” the silent system, producing a completely new molecule.

The resulting compound formed a lasso-like loop, a rare 3-dimensional structure that makes it highly stable and resistant to breakdown by enzymes or heat.

How It Works

Lariocidin doesn’t attack bacterial cell walls like penicillin, nor block protein synthesis like tetracyclines.Instead, it binds to a previously unknown site on the bacterial ribosome, disrupting how bacteria build essential proteins.

Because human ribosomes differ significantly, Lariocidin shows no measurable toxicity in human cells. A rare and valuable property for an antibiotic. In infected mice, a single therapeutic dose of Lariocidin markedly reduced bacterial load and improved survival within 24 hours.

How the Study Was Done

Metagenomic sequencing of thousands of soil bacteria to locate unusual biosynthetic gene clusters.
Heterologous expression in a model organism (Streptomyces coelicolor) to trigger production.
AI-assisted structural prediction to model folding and chemical properties.
Functional testing against 40 bacterial strains, including WHO-listed “critical priority” pathogens.
Safety and pharmacology in cell cultures and mouse infection models.

The approach blends traditional microbiology with digital biology, accelerating what once took years into months.

Key Findings

Broad activity: effective against Gram-positive and Gram-negative bacteria, including carbapenem-resistant strains.
High stability: remains active under body temperature, acidic pH, and even boiling water.
Slow resistance development: bacteria took 10× longer to develop resistance compared to standard antibiotics.
No observed human-cell toxicity at therapeutic doses.

Limitations and Next Steps

Human clinical data are still missing; Phase I safety trials are the next step.
Natural yields are extremely low. Industrial production will require synthetic biology or fermentation engineering.
Like most antibiotics, overuse could still drive resistance; stewardship programs will be essential.

Why This Matters for Switzerland

Switzerland has both the expertise and infrastructure to translate such discoveries into real therapies.

With resistant infections on the rise in Swiss hospitals (especially in intensive care) a molecule like Lariocidin could:

reduce treatment costs for complex infections,
shorten hospital stays, and
relieve public health spending pressures on insurers.

It also opens up an opportunity for Swiss biotech start-ups to focus on AI-driven antibiotic discovery, an area currently seeing renewed investor attention.

Economic and Insurance Implications

For health and re-insurers, the implications are double-edged:

Positive: fewer complications, shorter hospitalisations, lower infection-related mortality.
Challenging: early-stage treatments like Lariocidin will be expensive (CHF 10 000–20 000 per course) and may require new reimbursement models.
Strategic: insurers may shift toward “value-based” coverage, paying for effectiveness rather than drug volume.

This aligns with Switzerland’s broader push toward high-value care and prevention-oriented healthcare funding.

Overall Assessment

Lariocidin is a reminder that nature’s chemical diversity remains vastly untapped, and that AI can help us navigate it.It combines the elegance of natural evolution with the precision of modern computation.

If it passes clinical testing, it could redefine antibiotic R&D. Not as a random hunt, but as a guided search through the planet’s genomic memory.

What Comes Next

Scale-up: engineering bacteria or yeast to produce Lariocidin at industrial yield.
Human safety testing: evaluating pharmacokinetics and potential side effects.
Global policy: pushing for antibiotic “subscription” models to ensure innovation stays profitable.

In the age of resistance, this soil-born peptide may mark the beginning of a new antibiotic era, one where innovation comes not from luck, but from decoding nature’s own blueprints.

Reference

Jangra M, Travin DY, Aleksandrova EV, Kaur M, Darwish L, Koteva K, Klepacki D, Wang W, Tiffany M, Sokaribo A, Chen X, Deng Z, Tao M, Coombes BK, Vázquez-Laslop N, Polikanov YS, Mankin AS, Wright GD. A broad-spectrum lasso peptide antibiotic targeting the bacterial ribosome. Nature. 2025 Apr;640(8060):1022-1030. doi: 10.1038/s41586-025-08723-7. Epub 2025 Mar 26. Erratum in: Nature. 2025 Sep;645(8082):E11. doi: 10.1038/s41586-025-09597-5. PMID: 40140562; PMCID: PMC12497486. Link