The xaxAB genes encoding a new apoptotic toxin from the insect pathogen Xenorhabdus nematophila are present in plant and human pathogens.
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 Brehélin, M. (2003) J. Biol. 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 C1. 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.
Vigneux
Fabienne
F
Ecologie Microbienne des Insectes et Interactions Hôte-Pathogène, Unité Mixte de Recherche 1133, Institut National de la Recherche Agronomique-Université de Montpellier II, 34095 Montpellier, France.
Zumbihl
Robert
R
Ecologie Microbienne des Insectes et Interactions Hôte-Pathogène, Unité Mixte de Recherche 1133, Institut National de la Recherche Agronomique-Université de Montpellier II, 34095 Montpellier, France.
Jubelin
Grégory
G
Ecologie Microbienne des Insectes et Interactions Hôte-Pathogène, Unité Mixte de Recherche 1133, Institut National de la Recherche Agronomique-Université de Montpellier II, 34095 Montpellier, France.
Ribeiro
Carlos
C
Ecologie Microbienne des Insectes et Interactions Hôte-Pathogène, Unité Mixte de Recherche 1133, Institut National de la Recherche Agronomique-Université de Montpellier II, 34095 Montpellier, France.
Poncet
Joël
J
Unité Mixte de Recherche CNRS 5203, INSERM U661, Université de Montpellier I et II, 34094 Montpellier, France.
Baghdiguian
Stephen
S
Institut des Sciences de l'Evolution, Unité Mixte de Recherche 5554 CNRS-Université de Montpellier II, 34095 Montpellier, France.
Givaudan
Alain
A
Ecologie Microbienne des Insectes et Interactions Hôte-Pathogène, Unité Mixte de Recherche 1133, Institut National de la Recherche Agronomique-Université de Montpellier II, 34095 Montpellier, France. Electronic address: givaudan@univ-montp2.fr.
Brehélin
Michel
M
Ecologie Microbienne des Insectes et Interactions Hôte-Pathogène, Unité Mixte de Recherche 1133, Institut National de la Recherche Agronomique-Université de Montpellier II, 34095 Montpellier, France. Electronic address: brehelin@univ-montp2.fr.
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics*; D001427:Bacterial Toxins / Q000737:chemistry / Q000235:genetics*; D005798:Genes, Bacterial / Q000502:physiology; D006367:HeLa Cells; D006434:Hemocytes / Q000737:chemistry / Q000382:microbiology; D006460:Hemolysin Proteins / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D019476:Insect Proteins / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D009336:Necrosis; D010940:Plant Proteins / Q000737:chemistry / Q000235:genetics*; D010944:Plants / Q000382:microbiology*; D011513:Proteus mirabilis / Q000235:genetics; D044224:Pseudomonas syringae / Q000235:genetics; D018411:Spodoptera / Q000382:microbiology*; D020593:Xenorhabdus / Q000737:chemistry / Q000235:genetics* / Q000472:pathogenicity; D015008:Yersinia enterocolitica / Q000235:genetics
D001426:Bacterial Proteins; D001427:Bacterial Toxins; D006460:Hemolysin Proteins; D019476:Insect Proteins; D010940:Plant Proteins; C519450:alpha-xenorhabdolysin, Xenorhabdus nematophila