Xenorhabdus nematophila (enterobacteriacea) secretes a cation-selective calcium-independent porin which causes vacuolation of the rough endoplasmic reticulum and cell lysis

Abstract

Xenorhabdus nematophila and Photorhabdus luminescens are two related enterobacteriaceae studied for their use in biological control and for synthesis of original virulence factors and new kinds of antibiotics. X. nematophila broth growth exhibits different cytotoxic activities on insect (Spodoptera littoralis, lepidoptera) immunocytes (hemocytes). Here we report the purification of the flhDC-dependent cytotoxin, a 10,790-Da peptide we have called α-Xenorhabdolysin (αX). We show that plasma membrane of insect hemocytes and of mammal red blood cells is the first target of this toxin. Electrophysiological and pharmacological approaches indicate that the initial effect of αX on macrophage plasma membrane is an increase of monovalent cation permeability, sensitive to potassium channel blockers. As a consequence, several events can occur intracellularly, such as selective vacuolation of the endoplasmic reticulum, cell swelling, and cell death by colloid-osmotic lysis. These effects, inhibited by potassium channel blockers, are totally independent of Ca2+. However, the size of the pores created by αX on macrophage or red blood cell plasma membrane increases with toxin concentration, which leads to a rapid cell lysis.