Monalysin, a Novel ß-Pore-Forming Toxin from the Drosophila Pathogen Pseudomonas entomophila, Contributes to Host Intestinal Damage and Lethality

PLoS Pathogens

Isabelle Vallet-Gély¹  Ioan Iacovache²  Onya Opota²  Manuel Rodrigo Gonzalez²  Françoise-Gisou van der Goot²  Bruno Lemaitre²  Renaud Vincentelli³  Alain Roussel³  Christine Kellenberger³ 

[1] Centre de Génétique Moléculaire, CNRS, Gif-sur-Yvette, France;Global Health Institute, Ecole Polytechnique Fédérale Lausanne (EPFL), Lausanne, Switzerland;Structural Immunology, AFMB UMR 6098 CNRS/UI/UII, Case 932, Marseille, France

关键词: Drosophila melanogaster;    Toxins;    Gastrointestinal tract;    Virulence factors;    Cell staining;    Pseudomonas putida;    Acridines;    Homeostasis;   

DOI  :  10.1371/journal.ppat.1002259

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Pseudomonas entomophila is an entomopathogenic bacterium that infects and kills Drosophila. P. entomophila pathogenicity is linked to its ability to cause irreversible damages to the Drosophila gut, preventing epithelium renewal and repair. Here we report the identification of a novel pore-forming toxin (PFT), Monalysin, which contributes to the virulence of P. entomophila against Drosophila. Our data show that Monalysin requires N-terminal cleavage to become fully active, forms oligomers in vitro, and induces pore-formation in artificial lipid membranes. The prediction of the secondary structure of the membrane-spanning domain indicates that Monalysin is a PFT of the ß-type. The expression of Monalysin is regulated by both the GacS/GacA two-component system and the Pvf regulator, two signaling systems that control P. entomophila pathogenicity. In addition, AprA, a metallo-protease secreted by P. entomophila, can induce the rapid cleavage of pro-Monalysin into its active form. Reduced cell death is observed upon infection with a mutant deficient in Monalysin production showing that Monalysin plays a role in P. entomophila ability to induce intestinal cell damages, which is consistent with its activity as a PFT. Our study together with the well-established action of Bacillus thuringiensis Cry toxins suggests that production of PFTs is a common strategy of entomopathogens to disrupt insect gut homeostasis.

【 授权许可】

CC BY