Study of insect-killing bacteria examines how peptide diversity could aid antibiotic development

A new study examined bacteria that live in tiny worms that kill insects, and it could help develop new antibiotics, according to a report by Interesting Engineering. Researchers at the Max Planck Institute for Terrestrial Microbiology and the University of Marburg studied how these bacteria produce different versions of GameXPeptides, which kill insects. The study, published in Nature Ecology & Evolution, investigated how these bacterial compounds evolved, as changes in the bacteria's DNA over time altered the GameXPeptides.

According to the study, researchers examined GameXPeptides in Xenorhabdus and Photorhabdus bacteria that live with tiny worms called nematodes. When nematodes enter 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 investigate how different peptide structures evolved. The study identified 49 compounds, including side products.

The study continued that natural selection, genetic drift, and recombination biases shape the evolution of nonribosomal peptides, a class of compounds used in antibiotics such as penicillin, as well as toxins. Scientists found three forces that help to explain why different versions of GameXPeptide exist. But natural selection alone does not account for the diversity of these compounds. Random mutations and genetic exchange also shape which variants emerge.

The study examined one family of peptide-producing enzymes. The researchers said further work would be needed to determine whether the same evolutionary principles apply to peptides that humans use in medicine. However, that being said, many antibiotics are nonribosomal peptides. Helge Bode of the Max Planck Institute for Terrestrial Microbiology said in Phys that their results show that the conceptual framework they developed for the GameXPeptides can serve as a guide to decipher the evolutionary forces acting on other natural product families, such as the polyketide synthases, which like NRPS, produce many clinically relevant natural products.