The xaxAB genes encoding a new apoptotic toxin from the insect pathogen Xenorhabdus nematophila are present in plant and human pathogens

Fabienne Vigneux (1) , Robert Zumbihl (1) , Grégory Jubelin (1) , Carlos Ribeiro (1) , Joël Poncet (2) , Stephen Baghdiguian (3) , Alain Givaudan (1) , Michel Brehélin (1)

1 EMIP - Ecologie microbienne des insectes et interactions hôte-pathogène
2 IGF - Institut de Génomique Fonctionnelle
3 UMR ISEM - Institut des Sciences de l'Evolution de Montpellier

Xenorhabdus nematophila, a member of the Enterobacteriaceae, kills many species of insects by strongly depressing the immune system and colonizing the entire body. A peptide cytotoxin has been purified from X. nematophila broth growth, and the cytolytic effect on insect immunocytes and hemolytic effect on mammalian red blood cells of this toxin have been described (Ribeiro, C., Vignes, M., and Brehelin, M. (2003) J. Mal. Chem. 278, 3030-3039). We show here that this toxin, Xenorhabdus alpha-xenorhabdolysin (Xax), triggers apoptosis in both insect and mammalian cells. We also report the cloning and sequencing of two genes, xaxAB, encoding this toxin in X. nematophila. The expression of both genes in recombinant Escherichia coli led to the production of active cytotoxin/hemolysin. However, hemolytic activity was observed only if the two peptides were added in the appropriate order. Furthermore, we report here that inactivation of xaxAB genes in X. nematophila abolished the major cytotoxic activity present in broth growth, called C I. We also show that these genes are present in various entomopathogenic bacteria of the genera Xenorhabdus and Photorhabdus, in Pseudomonas entomophila, in the human pathogens Yersinia enterocolitica and Proteus mirabilis, and in the plant pathogen Pseudomonas syringae. This toxin cannot be classified in any known family of cytotoxins on the basis of amino acid sequences, locus organization, and activity features. It is, therefore, probably the prototype of a new family of binary toxins.

Mots clés: BACTERIUM PHOTORHABDUS-LUMINESCENS; ESCHERICHIA-COLI; GENOME SEQUENCE; FULL VIRULENCE; FAMILY; CELLS; HEMOLYSIN; CLOSTRIDIUM; ACTIVATION; EXPRESSION

Domaines: Biodiversité et Ecologie

Fabienne Vigneux, Robert Zumbihl, Grégory Jubelin, Carlos Ribeiro, Joël Poncet, et al.. The xaxAB genes encoding a new apoptotic toxin from the insect pathogen Xenorhabdus nematophila are present in plant and human pathogens. Journal of Biological Chemistry, 2007, 282 (13), pp.9571-9580. ⟨10.1074/jbc.M604301200⟩. ⟨halsde-00366228⟩