Newswise – Animals and humans coexist with a vast array of microbes known as the microbiome, forming a complex relationship that can range from mutually beneficial to pathogenic. To protect against harmful pathogens and maintain the presence of beneficial microorganisms, animals have developed various defenses.
One of them is small antimicrobial peptides (AMPs); Small peptides that fight against invading microbes. AMPs are critical immunomodulators in plants and animals, fighting potential infections and influencing the composition of the host’s microbiome.
Although previous studies have shown that AMPs evolve rapidly, little is known about the driving forces behind this evolution. For example, different animals have different “pools” of AMP genes, while others are not found anywhere else. Understanding the evolutionary “logic” behind this is important not only as an ecological study, but also for developing innovative strategies to prevent infection by targeting specific microbial threats.
Now, a study led by three scientists at EPFL is uncovering the selective pressures that drive the evolution of AMPs and how they regulate bacteria in the host’s microbiome. The work was carried out by Bruno Lemaitre’s group at EPFL’s School of Life Sciences, led by Mark Hanson (now at the University of Exeter) and Lena Grolms. Publishes in science.
The researchers focused on diptericin (Dpt), a small antimicrobial peptide that primarily protects flies against Gram-negative bacteria by disrupting their bacterial membrane. Looking at the fruit fly Drosophila, the team looked at how diptericins function and evolve in response to their microbial environment.
The team found that different types of diptericins, known as DptA and DptB, play specific roles in the fruit fly’s defense against different bacteria.
By testing Drosophila mutants lacking specific AMP gene families, the researchers found that DptA was effective against DptA. Providencia retgeri, a natural pathogen of Drosophila. Meanwhile, DptB helped the host to resist infection by multiple species Acetobacter, some of which reside in the gut of Drosophila and support its physiology and development. In contrast, it did not play a significant role against DptA Acetobacter DptB did not play a significant role against them Providencia.
Analyzing the evolutionary history of diptericin genes, the scientists found two examples of convergent evolution, leading to DPTB-like genes in fruit flies, which feed on high amounts of fruit. Acetobacter. This suggests that DptB has evolved to regulate Acetobacter Ancestral fruit-feeding in Drosophila.
The study also found that flies with different ecological niches, such as mushroom-feeding or plant-parasitic, lost either the DptB gene or both the DptA and DptB genes. Acetobacter or both Providencia And Acetobacterrespectively.
Meanwhile, variations in DptA and DptB sequences have been found to predict host resistance to infection by these bacteria across the Drosophila genus. This highlights the evolutionary adaptation of the fly’s immune system to combat specific microbes prevalent in the environment.
To validate their findings, the researchers infected different Drosophila species with different variants of the DptA and DptB genes. The results were striking: the host’s resistance to infection P. retgeri And Acetobacter This was easily predicted across fly species separated by nearly 50 million years of evolution, using the presence and polymorphism of the DptA or DptB genes.
This work sheds light on the dynamics that shape the host’s immune system and how the host’s defenses adapt to combat specific pathogens while nurturing beneficial microbes. The findings suggest a new model of AMP-microbiome evolution, involving gene duplication, sequence convergence, and gene loss, all of which are driven by the host’s environment and microbiome. This model explains why different species have distinct repertoires of AMPs, offering insights into how host immune systems rapidly adapt to a suite of microbes associated with a new ecological niche.
“The way our bodies fight infections is very complex,” says Mark Hanson. “But this kind of research helps us see our immune system in a new light. ‘Why is our immune system the way it is?’ That will help us understand how to fight infections, including those that are resistant to antibiotics.