α2-macroglobulin function of thioester-containing proteins guards Drosophila from a bacterial protease via two immune-induced peptides

• 成果类型: Article
• 署名作者: Cai, Chuping; Acker, Adrian; Huang, Jianqiong; Liu, Yingying; Molino, Maria Victoria; Mariscotti, Javier F.; Garcia-Vescovi, Eleonora; Bulet, Philippe; Hammann, Philippe; Chicher, Johana; Liegeois, Samuel; Li, Zi; Hoffmann, Jules A.; Matt, Nicolas; Ferrandon, Dominique
• 署名单位: Guangzhou Medical University; Universites de Strasbourg Etablissements Associes; Universite de Strasbourg; Institut National de la Sante et de la Recherche Medicale (Inserm); Centre National de la Recherche Scientifique (CNRS); Universites de Strasbourg Etablissements Associes; Universite de Strasbourg; National University of Rosario; Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET); Centre National de la Recherche Scientifique (CNRS); Institut National de la Sante et de la Recherche Medicale (Inserm); Communaute Universite Grenoble Alpes; CNRS - National Institute for Biology (INSB); Universite Grenoble Alpes (UGA); Centre National de la Recherche Scientifique (CNRS); Universites de Strasbourg Etablissements Associes; Universite de Strasbourg; Universites de Strasbourg Etablissements Associes; Universite de Strasbourg; Institut National de la Sante et de la Recherche Medicale (Inserm); Communaute Universite Grenoble Alpes; Centre National de la Recherche Scientifique (CNRS); Universite Grenoble Alpes (UGA); CNRS - National Institute for Biology (INSB)
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2525580123
• 发表日期: 2026-01-27
• 页码: e2525580123
• 关键词: innate immunity; resilience/disease tolerance; host defense micropeptides; lncRNAs; protease inhibitor function modulation; antimicrobial peptides; toll; identification; melanization; melanogaster

摘要

RNAseq analysis of the Drosophila genome has revealed further immune-induced genes. Two genes initially annotated as lncRNAs, CG44404(yul & uuml;) and CG45045(shenshu), are strongly induced. We report here that these two genes actually encode highly related secreted peptides found in the Sophophora subgenus of Drosophila species. We have generated single and double null mutants of these loci and found that the double mutant line did not display any enhanced susceptibility to an immune challenge with a panel of bacterial and fungal pathogens, except for Pseudomonas aeruginosa. We did not observe any increased P. aeruginosa burden in yul & uuml;-shenshu mutants, suggesting that the two peptides may not be required for resistance to infection. Rather, we find that they provide a level of protection against Outer Membrane Vesicles (OMVs) purified from either P. aeruginosa or Serratia marcescens culture supernatants. We have recently reported that S. marcescens OMVs induce the paralysis of flies through the induction of apoptosis in at least some neurons. Much of the virulence of these OMVs is mediated by the metalloprotease PrtA. While Yul & uuml;/Shenshu do not display any protease inhibition activity, the detection of an association between Yul & uuml; and the Drosophila complement thioester-containing protein 2 (Tep2) led to the finding that both Tep2 and Tep4 mutants are sensitive to the injection of PrtA while their overexpression significantly protects wild-type flies from the effects of this protease. Both Tep2 and Tep4 are able to inhibit the activity of PrtA in a thioester-and yul & uuml;/shenshu-dependent manner. Thus, these Teps may also function as alpha 2-macroglobulins.