Newswise — Animals and humans coexist alongside a diverse array of microorganisms, collectively known as the microbiome. This intricate relationship can range from being mutually beneficial to potentially harmful due to pathogenic microbes. To counteract the risks posed by harmful pathogens and to maintain the presence of beneficial microorganisms, animals have developed various defense mechanisms.
One such defense mechanism involves the use of small antimicrobial peptides (AMPs), which are small peptides that combat invading microbes. AMPs play a critical role as immune effectors in both plants and animals, helping to fend off potential infections while also influencing the composition of the host's microbiome.
Despite previous studies demonstrating the rapid evolution of AMPs, the underlying driving forces behind this evolutionary process remained largely unknown. Different animals possess distinct "repertoires" of AMP genes, while lacking others that may be found elsewhere. Unraveling the evolutionary logic behind these differences is not only important for ecological research but also holds promise for the development of innovative strategies aimed at preventing infections by specifically targeting microbial threats.
A recent study conducted by three scientists at EPFL sheds light on the selective pressures driving the evolution of antimicrobial peptides (AMPs) and their role in controlling bacteria within the host's microbiome. Led by Mark Hanson (currently at the University of Exeter), Lena Grollmus, and conducted within Bruno Lemaitre's group at EPFL's School of Life Sciences, the research findings are published in Science.
The researchers focused on Diptericin (Dpt), a small antimicrobial peptide primarily responsible for defending flies against Gram-negative bacteria by disrupting their bacterial membrane. Using the fruit fly Drosophila as their model, the team investigated how Diptericins function and evolve in response to the microbial environment.
Through their investigations, the team uncovered that there are different variants of Diptericins, specifically DptA and DptB, each serving specific roles in the fruit fly's defense against different types of bacteria.
To understand their individual functions, the researchers screened Drosophila mutants lacking specific AMP gene families. They found that DptA proved effective against Providencia rettgeri, a natural pathogen of Drosophila. On the other hand, DptB played a vital role in helping the host resist infections caused by various species of Acetobacter, some of which reside in Drosophila's gut, supporting its physiology and development. Interestingly, DptA showed no significant impact against Acetobacter, while DptB did not have a significant effect against Providencia. This highlights the specificity of each Diptericin variant in countering particular bacterial threats.
Upon analyzing the evolutionary history of the Diptericin genes, the researchers made two notable discoveries of convergent evolution events that resulted in the emergence of DptB-like genes in fruit flies that predominantly feed on fruits. This observation is particularly significant since such an environment is associated with high levels of Acetobacter. This suggests that the evolution of DptB was driven by the need to control Acetobacter in the ancestral fruit-feeding Drosophila.
Additionally, the study revealed intriguing patterns among fruit flies with different ecological niches. For instance, those that primarily fed on mushrooms or acted as plant-parasites had either lost the DptB gene or both DptA and DptB genes, respectively. This loss corresponded to the absence of Acetobacter or both Providencia and Acetobacter in their microbiome, signifying a specialization of the fly's immune system according to their specific habitats.
Furthermore, the research identified variations in DptA and DptB sequences that could predict the host's resistance to infection by bacteria within the Drosophila genus. This finding highlights the remarkable evolutionary adaptation of the fly's immune repertoire, tailored to combat specific microbes prevalent in their respective surroundings. In essence, fruit flies have developed a finely tuned immune defense system that aligns with the unique challenges posed by their ecological environments.
To validate their discoveries, the researchers conducted experiments by infecting various Drosophila species with different variants of DptA and DptB genes. The results were remarkable, as they found that the host's resistance to infection by both P. rettgeri and Acetobacter could be accurately predicted based solely on the presence and genetic variation of DptA or DptB genes. Remarkably, this prediction held true even across fly species that had diverged nearly 50 million years ago during evolution.
The study provides crucial insights into the underlying dynamics that shape the host's immune system and how it adapts to effectively combat specific pathogens while nurturing beneficial microorganisms. The findings propose a novel model of AMP-microbiome evolution, which encompasses gene duplication, sequence convergence, and gene loss, all guided by the host's unique ecological environment and microbiome. This model helps elucidate why different species possess distinct repertoires of AMPs, providing valuable knowledge on how host immune systems rapidly adjust to the array of microbes present in new ecological niches.
Mark Hanson emphasizes the complexity of our bodies' fight against infections and highlights that this research opens up new perspectives on understanding the immune system. By examining why our immune system is structured the way it is, this knowledge can contribute to developing effective strategies to combat infections, including those that have developed resistance to antibiotics. The study offers promising avenues for advancing our understanding of immunity and improving approaches to tackling challenging infections.
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