A new study examined bacteria that reside within small worms capable of killing insects, revealing that this relationship could aid in the development of new antibiotics.
According to ISNA, researchers from the Max Planck Institute for Terrestrial Microbiology and the University of Marburg investigated how these bacteria produce various versions of "GameXPeptides"—compounds that kill insects.
The study, published in the journal *Nature Ecology & Evolution*, explored the evolution of these bacterial compounds, noting that changes in the bacteria's DNA over time led to alterations in the GameXPeptides. This diversity holds potential for the development of new drugs, as these peptides belong to a broader class known as non-ribosomal peptides.
How do bacteria develop diverse chemical weapons?
According to the study, researchers examined GameXPeptides in *Xenorhabdus* and *Photorhabdus* bacteria, which live in association with small worms called nematodes. When these nematodes enter an insect host, the bacteria are released and produce compounds that kill the host.
The research team reconstructed the evolutionary history of GxpS—the enzyme responsible for producing GameXPeptides—to understand how the various peptide structures evolved. The study identified 49 such compounds, including various byproducts. Georg Hochberg, a researcher at the University of Marburg, remarked: "This was like a game of five-dimensional chess." Frequent recombination obscures the evolutionary history of these enzymes. Each recombination event rewrites a portion of their past—yet it is precisely this complexity that makes the system so fascinating.
The study further notes that natural selection, genetic drift, and recombination biases shape the evolution of non-ribosomal peptides—a class of compounds found in substances ranging from antibiotics like penicillin to various toxins.
As the study suggests, a better understanding of the mechanisms underlying the diversity of bacterial natural products could pave the way for the discovery of new antibiotics capable of overcoming existing resistance.
Scientists identified three forces that help explain the existence of various versions of "GameXPeptide." Gaining insight into these processes could assist researchers in discovering other variants of non-ribosomal peptides.
Naturally, natural selection alone does not account for the diversity of these compounds; random mutations and genetic exchange also shape the nature of the emerging variants. When DNA is exchanged or rearranged—a process known as "recombination"—it gives rise to new genetic combinations.
The researchers identified 27 "synonymous" recombination events—which did not alter the peptide structures—and 26 "non-synonymous" events, which had the potential to modify them. The team also discovered that recombination is more likely to occur between enzymatic domains that share similar DNA sequences, particularly within the same gene. This bias constrained the range of peptide variants that could emerge through recombination.
These findings could inform future research on antibiotics.
The study examined a family of peptide-producing enzymes. The researchers note that further work is required to determine whether the same evolutionary principles apply to the peptides used in human medicine.
Nevertheless, many antibiotics are non-ribosomal peptides. The researchers may have opened a new avenue of exploration, enabling scientists to investigate novel antibiotics.
Helge Bode, from the Max Planck Institute for Terrestrial Microbiology, stated: "Our results suggest that the conceptual framework we developed for GameXPeptides can serve as a guide for deciphering the evolutionary forces acting on other families of natural products—such as polyketide synthases, which, like NRPS, produce many clinically relevant natural products."
By understanding how these products evolve and diversify within bacteria, scientists may be better equipped to address the resistance that has emerged against some existing antibiotics.