A species of Paenibacillus bacteria has potent antibacterial activity against some pathogenic bacteria such as Escherichia coli.Credit: Clouds Hill Imaging Ltd/Science Photo Library
Researchers have discovered a new antibiotic molecule that targets a broad range of disease-causing bacteria — even strains resistant to commercial drugs — and is not toxic to human cells1.
The molecule was found in soil samples collected from a laboratory technician’s garden. The discovery shows that “there is terrifically interesting stuff hiding in plain sight”, says Kim Lewis, a microbiologist at Northeastern University in Boston, Massachusetts, who was not involved in the research. “Kudos to them that they knew what to look for.”
The latest molecule targets bacteria’s protein-making factory, the ribosome, in a way that other antibiotic drugs don’t. The ribosome is an attractive antibiotic target because bacteria don’t easily develop resistance to drugs targeting the structure, adds Lewis.
The search for new antibiotics is necessary because bacteria acquire resistance to existing drugs with continued use. In 2021, bacterial resistance to antimicrobial drugs was associated with 1.1 million deaths globally, a figure that could increase to 1.9 million by 2050.
“The antibiotic-resistance crisis is an existential threat to medicine,” says Gerry Wright, a chemical biologist at McMaster University in Hamilton, Canada, and a co-author of the study, which is published in Nature today.
Garden-variety bacteria
Wright and his colleagues set out to find microbes that have developed previously unknown tricks to kill pathogens. They collected soil samples in Petri dishes with growth medium and stored them for a year. The researchers then exposed the microbes from these samples to Escherichia coli, a common gut bacterium that can cause serious disease.
One sample showed potent antibacterial activity — by a species belonging to the genus Paenibacillus.
Further rounds of screening, genome sequencing and structural analysis revealed that the bacterium produces a molecule that belongs to a group of peptides that form a lasso-shaped knot. These peptides are known for being robust and can probably even survive being digested. “It’s a nice, really compact and incredibly robust structure,” says Wright.
The molecule, which the researchers named lariocidin, binds to the ribosome and also to transfer RNA, which supplies the ribosome with the amino-acid building blocks it needs to string together peptide chains. By doing so, it prevents the genetic code from being read correctly, and also corrupts the code, jumbling the output. Ultimately, this means that the ribosome produces incorrect peptides, some of which probably end up being toxic to the bacterium and killing it, says Lewis. And because lariocidin uses a different mode of action to other antibiotics, pathogens haven’t already developed resistance to it, he adds.
