A new study examined bacteria that live in tiny worms that kill insects and could help develop new antibiotics.
Researchers at the Max Planck Institute for Terrestrial Microbiology and the University of Marburg studied how these bacteria produce different versions of GameX peptides that kill insects.
The study, published in Nature, ecology and evolution, studied how these bacterial compounds evolved, as changes in the bacteria’s DNA over time altered the GameXPeptides. This diversity could lead to new drugs because these peptides belong to a broader class called nonribosomal peptides.
How bacteria develop various chemical weapons
According to the study, researchers examined GameXPeptides in Xenorhabdus And Photorhabdus Bacteria that live with tiny worms called nematodes.
When nematodes invade an insect host, the bacteria are released and produce these compounds that kill it.
The team reconstructed the evolutionary history of GxpS, the enzyme that produces GameXPeptides, to study how different peptide structures evolved. The study identified 49 compounds, including byproducts.
“It felt like you were playing five-dimensional chess,” said Georg Hochberg, a researcher at the University of Marburg Physics.
“Frequent recombination obscures the evolutionary history of these enzymes – each recombination event overwrites part of their past. But it is precisely this complexity that makes the system so fascinating.”
The study further stated that natural selection, genetic drift and recombination bias influence the evolution of nonribosomal peptides, a class of compounds used in antibiotics such as penicillin and toxins.
“If we better understand the mechanisms underlying bacterial natural product diversity, it may be possible to discover new antibiotics that overcome existing resistance,” the study says.
Scientists have found three forces that explain why there are different versions of GameXPeptide. Understanding these processes could help scientists discover other versions of other nonribosomal peptides.
But natural selection alone does not explain the diversity of these compounds. Random mutations and genetic exchange also determine which variants emerge. When DNA is exchanged or rearranged, new genetic combinations are created, a process called recombination.
The researchers identified 27 synonymous recombination events that did not change the peptide structures and 26 non-synonymous events that could change them.
The team also found that recombination was more likely between enzyme domains with similar DNA sequences, particularly within the same gene. This bias limited which peptide variants could arise through recombination.
The findings could be incorporated into future antibiotic research
The study examined a family of peptide-producing enzymes. The researchers said more work is needed to determine whether the same evolutionary principles apply to peptides that people use in medicine.
However, many antibiotics are nonribosomal peptides. These researchers may have opened a research avenue that could allow scientists to study new antibiotics.
“Our results show that the conceptual framework we developed for the GameXPeptides can serve as a guide for deciphering the evolutionary forces that act on other families of natural products, such as the polyketide synthases, which, like NRPS, produce many clinically relevant natural products,” said Helge Bode from the Max Planck Institute for Terrestrial Microbiology physics.
By understanding how these products evolve and diversify in bacteria, scientists may be able to combat the current resistance that humans have developed to some of the existing antibiotics.
