2023-08-04 スイス連邦工科大学ローザンヌ校(EPFL)
◆研究者は、ショウジョウバエを用いて、果糖という小さな抗微生物ペプチドに焦点を当て、その進化について調査しました。ショウジョウバエは、果糖に対して効果的な果糖DptAとDptBという2つの異なる種類のAMPsを持ち、それぞれが異なるバクテリアに対して特定の役割を果たすことがわかりました。
◆この研究により、感染に対抗する方法を理解し、特に抗生物質に耐性を持つ感染症に対処するための新たな知見を得る上で重要な貢献をしています。また、ホストの免疫系がマイクロバイオームに適応する仕組みを理解することで、感染に対する革新的な戦略の開発にも寄与する可能性が示されています。
<関連情報>
- https://actu.epfl.ch/news/how-the-microbiome-drives-the-evolution-of-immune-/
- https://www.science.org/doi/10.1126/science.adg5725
生態に関連した細菌がショウジョウバエの宿主抗菌ペプチドの進化を促す Ecology-relevant bacteria drive the evolution of host antimicrobial peptides in Drosophila
M. A. Hanson,L. Grollmus, and B. Lemaitre
Science Published:21 Jul 2023
DOI:https://doi.org/10.1126/science.adg5725
Editor’s summary
To prevent gut microbiota from running amok, animals and plants secrete a series of small, often multifunctional peptides called antimicrobial peptides. Until recently, antimicrobial peptides were considered to have broad activities, and it was unclear why such molecules showed signs of rapid evolution. Hanson et al. found a striking specificity for the peptides diptericin A and B for two species of gut commensal bacteria. These species occur in the natural environment of fruit flies depending on the food resource exploited: fruit or fungi. Thus, the presence or absence of diptericin A or B predicts the ecology of the fly. This work shows how an organism’s microbiota might be able to shape the host’s immune responses in a manner similar to how a host’s immune responses shape its microbiota. —Caroline Ash
Structured Abstract
INTRODUCTION
Antimicrobial peptides (AMPs) are host-encoded immune effectors first characterized for their role in fighting infection. AMPs are also important in determining the composition of the host microbiome in both plants and animals. Although many studies have shown rapid evolution of AMPs, little is known about the selective pressures driving that evolution.
RATIONALE
The host microbiome should exert a substantial selective pressure on host immune molecules because the host must maintain a delicate balance with its microbial associates. Variation in a single AMP can upset this balance, as suggested by recent investigations across diverse taxa. In Drosophila, previous studies have shown the AMP family Diptericin (Dpt) evolves rapidly, including a major effect of the amino acid polymorphism S69R of DptA on host defense against the opportunistic pathogen Providencia rettgeri, and Providencia spp. are commonly found in fly microbiome communities. Beneficial bacteria of the host microbiome also grow out of control in flies lacking multiple AMP gene families, particularly the gut mutualist Acetobacter. Drosophila species encode two Diptericin genes, DptA and DptB, which are the product of an ancestral duplication stemming from a DptB-like gene. To test the idea that the host immune repertoire might be specifically evolved for controlling common microbiome bacteria, we screened recently made Drosophila AMP mutants for defense against infection by Acetobacter spp. to determine whether any of the AMP genes could explain how flies keep this mutualistic microbe under control.
RESULTS
We found that a single AMP gene, DptB, explains the host ability to resist infection by multiple Acetobacter species. This interaction is highly specific: We confirmed that DptA does not contribute to defense against Acetobacter, whereas DptB does not contribute to defense against P. rettgeri. We therefore determined the evolutionary history of the Diptericin locus, and performed a systematic review of microbiome literature of Drosophila and other Diptera. We realized that there have been at least two events of convergent evolution toward DptB-like genes in flies feeding on fruit, an ecology associated with high levels of Acetobacter. These observations suggest that DptB evolved to control Acetobacter in the fruit-feeding Drosophila ancestor. Moreover, flies that secondarily adopted a mushroom-feeding ecology have repeatedly lost their DptB genes, alongside an absence of Acetobacter in mushroom-breeding sites. A similar pattern of evolution is also seen in flies that have developed a plant-parasitic ecology, which have lost both DptA and DptB genes and have an ecology lacking both Providencia and Acetobacter. To investigate whether these AMP-microbe specificities are shared throughout Drosophila, we infected species from across the phylogeny with a diverse complement of DptA- and DptB-like genes and alleles. We included species with a diversity of DptA-like genes, and both Drosophila melanogaster and mushroom-feeding flies with or without DptB. Host resistance to infection by P. rettgeri and Acetobacter was readily predicted using just DptA or DptB presence and polymorphism status, even across fly species separated by about 50 million years of evolution.
CONCLUSION
Our study shows how two microbe-specific defences evolved due to an ancestral duplication producing two Diptericin genes. We describe a one-sided evolutionary dynamic wherein the host has adapted its immune repertoire to environmental microbes rather than coevolution of host and microbe. This finding helps to explain the evolutionary logic behind the bursts of rapid evolution common in AMP gene families across taxa. Our results also reveal why certain AMPs can have such disproportionate roles in defense against specific microbes: They were evolutionarily selected for that purpose. This realization suggests that the genome can encode “vestigial” immune effectors, AMPs evolved for defense against microbes that are no longer relevant to the host’s modern ecology. Thus, derivation and loss of microbe-specific effectors offers the immune system a highly effective mechanism for tailoring host defenses for control of ecologically relevant microbes.
Fruit fly experiments demonstrate that the host immune system is uniquely adapted to common environmental microbes.
Evolutionary selection can tailor host antimicrobial peptides (chains) to control specific microbiome bacteria. As a defense system common across plants and animals, variations in the repertoire of antimicrobial peptides are likely important as key risk factors for preventing infection by common ecological microbes. [Credit: Diego Galagovsky]
Abstract
Antimicrobial peptides are host-encoded immune effectors that combat pathogens and shape the microbiome in plants and animals. However, little is known about how the host antimicrobial peptide repertoire is adapted to its microbiome. Here, we characterized the function and evolution of the Diptericin antimicrobial peptide family of Diptera. Using mutations affecting the two Diptericins (Dpt) of Drosophila melanogaster, we reveal the specific role of DptA for the pathogen Providencia rettgeri and DptB for the gut mutualist Acetobacter. The presence of DptA- or DptB-like genes across Diptera correlates with the presence of Providencia and Acetobacter in their environment. Moreover, DptA- and DptB-like sequences predict host resistance against infection by these bacteria across the genus Drosophila. Our study explains the evolutionary logic behind the bursts of rapid evolution of an antimicrobial peptide family and reveals how the host immune repertoire adapts to changing microbial environments.
