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

Fiche publication

Date publication

janvier 2026

Journal

Proceedings of the National Academy of Sciences of the United States of America

Auteurs

Membres identifiés du Cancéropôle Est :
Mr HAMMANN Philippe

Tous les auteurs :
Cai C, Acker A, Huang J, Liu Y, Molino MV, Mariscotti JF, Garcia-Véscovi E, Bulet P, Hammann P, Chicher J, Liegeois S, Li Z, Hoffmann JA, Matt N, Ferrandon D

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/41564131

Résumé

RNAseq analysis of the genome has revealed further immune-induced genes. Two genes initially annotated as lncRNAs, () and (), are strongly induced. We report here that these two genes actually encode highly related secreted peptides found in the Sophophora subgenus of 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 . We did not observe any increased burden in 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 or culture supernatants. We have recently reported that 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 Yulü/Shenshu do not display any protease inhibition activity, the detection of an association between Yulü and the complement thioester-containing protein 2 (Tep2) led to the finding that both and 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 -dependent manner. Thus, these Teps may also function as α2-macroglobulins.