Bacillus thuringiensis targets the host intestinal epithelial junctions for successful infection of Caenorhabditis...

Pathogenic bacteria use different strategies to infect their hosts, including the simultaneous production of pore forming toxins and several virulence factors that may synergize their pathogenic effects. However, how the pathogenic bacteria are able to break out the host intestinal barrier is poorly understood. The infectious cycle of Bacillus thuringiensis (Bt) bacterium in Caenorhabditis elegans is a powerful model system to study the early stages of the infection process. Bt produces Cry pore-forming toxins during the sporulation phase that are key virulence factors involved in its pathogenesis. In this study, we show that Bt disrupts the intestinal epithelial junctions of C. elegans at early stages of infection allowing Bt bacterium to complete its life cycle in the worm. We further confirmed that the vegetative Bt cells trigger a quorum sensing response that is activated by PlcR regulator, resulting in production of different virulence factors, such as the metalloproteinases ColB and Bmp1, that besides Cry toxins are necessary to disrupt the nematode epithelial junctions causing efficient bacterial host infection and death of the nematode. Our work provides new insights into the pathogenesis of Bt and highlights the importance of breaking down host epithelial junctions for a successful infection. A similar mechanism could be used by other pathogen-host interactions since epithelial junctions are conserved structures from insects to mammals.