Scientists uncover how insect-killing bacteria could lead to new antibiotics

A new study examined bacteria that live in tiny worms that kill insects, and it 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 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. This diversity could lead to new medicines, as these peptides belong to a broader class called nonribosomal peptides.

How bacteria develop different chemical weapons

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.

“It felt like playing five-dimensional chess,” said Georg Hochberg, a researcher at the University of Marburg, in Phys.

“Frequent recombination obscures the evolutionary history of these enzymes—each recombination event overwrites a piece of their past. But it is precisely this complexity that makes the system so fascinating.”

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.

“If we better understand the mechanisms underlying bacterial natural product diversity, it may become possible to discover new antibiotics that overcome existing resistances,” as stated in the study.

Scientists found three forces that help to explain why different versions of GameXPeptide exist. Understanding these processes could help scientists discover other versions of other nonribosomal peptides.

But natural selection alone does not account for the diversity of these compounds. Random mutations and genetic exchange also shape which variants emerge. When DNA is exchanged or rearranged, it creates new genetic combinations, a process called recombination.

The researchers identified 27 synonymous recombination events that did not alter peptide structures and 26 nonsynonymous 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 emerge through recombination.

Findings could inform future antibiotic research

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. These researchers might have opened up an avenue to explore that might allow scientists to investigate new antibiotics.

“Our results show that the conceptual framework we 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,” Helge Bode of the Max Planck Institute for Terrestrial Microbiology said in Phys.

By understanding how these products evolve and diversify in bacteria, scientists might be able to tackle current resistance that humans have developed to some of the antibiotics that exist.

Source: https://interestingengineering.com/health/insect-killing-bacteria-antibiotics