The evolutionary novelty of insect defensins: from bacterial killing to toxin neutralization

• Published in: Cellular and molecular life sciences : CMLS 2024-12, Vol.81 (1), p.230-230, Article 230
• Main Authors: Gao, Bin, Zhu, Shunyi
• Format: Article
• Language: English
• Subjects: Amino Acid Motifs; Animals; Bacteria; Bacterial diseases; Bacterial infections; Bacterial Toxins - metabolism; Biochemistry; Biomedical and Life Sciences; Biomedicine; Cell Biology; Defensins; Defensins - chemistry; Defensins - genetics; Defensins - immunology; Deletion; Drosophila; Drosophila - classification; Drosophila - genetics; Drosophila - immunology; Drosophila - microbiology; Drosophila Proteins - genetics; Drosophila Proteins - immunology; Drosophila virilis; Effectors; Female; Fruit flies; Gene Deletion; Gene Duplication; Gram-positive bacteria; Infections; Innate immunity; Insects; Life Sciences; Microorganisms; Neutralization; Original Article; Pest resistance; Phylogeny; Protein Folding; Resilience; Staphylococcus aureus; Staphylococcus aureus - physiology; Structure-function relationships; Toxins
• ISSN: 1420-682X; 1420-9071
• DOI: 10.1007/s00018-024-05273-5

Insect host defense comprises two complementary dimensions, microbial killing-mediated resistance and microbial toxin neutralization-mediated resilience, both jointly providing protection against pathogen infections. Insect defensins are a class of effectors of innate immunity primarily responsible for resistance to Gram-positive bacteria. Here, we report a newly originated gene from an ancestral defensin via genetic deletion following gene duplication in Drosophila virilis , which confers an enhanced resilience to Gram-positive bacterial infection. This gene encodes an 18-mer arginine-rich peptide (termed Dvir ARP) with differences from its parent gene in its pattern of expression, structure and function. Dvir ARP specifically expresses in D. virilis female adults with a constitutive manner. It adopts a novel fold with a 3 10 helix and a two CXC motif-containing loop stabilized by two disulfide bridges. Dvir ARP exhibits no activity on the majority of microorganisms tested and only a weak activity against two Gram-positive bacteria. Dvir ARP knockout flies are viable and have no obvious defect in reproductivity but they are more susceptible to the Dvir ARP-resistant Staphylococcus aureus infection than the wild type files, which can be attributable to its ability in neutralization of the S. aureus secreted toxins. Phylogenetic distribution analysis reveals that Dvir ARP is restrictedly present in the Drosophila subgenus, but independent deletion variations also occur in defensins from the Sophophora subgenus, in support of the evolvability of this class of immune effectors. Our work illustrates for the first time how a duplicate resistance-mediated gene evolves an ability to increase the resilience of a subset of Drosophila species against bacterial infection.