As intracellular pathogens grow and develop inside a host organism they may utilize host resources to facilitate their growth. Microsporidia are a phylum of fungal-related obligate intracellular pathogens that infect all animal phyla including agriculturally relevant species such as honeybees and fish, yet little is known the host factors that are required for pathogen growth. We are studying a microsporidian pathogen called Nematocida parisii that naturally infects the C. elegans intestine. Recently we defined the C. elegans transcriptional response to N. parisii infection using RNAseq (Bakowski et al PLoS Pathogens, 2014), and have now used these data to identify predicted transcription factor binding sites upstream of pathogen-regulated genes. In these analyses we found an enrichment of binding sites for the transcription factor MDL-1, which is a member of the Mad-Max family of transcription factors. Animals defective for
mdl-1 are resistant to infection by N. parisii, indicating that
mdl-1 somehow promotes pathogen growth. Upon analyzing the other members of the conserved Mad-Max transcription factor family, we found that there appears to be a non-canonical rewiring of the pathway in its regulation of pathogen growth. Interestingly, we found that MDL-1 protein expression is induced upon infection and possibly leading to non-canonical Mad/Max signaling in response to infection. Overall these results provide a greater understanding of how obligate intracellular pathogens can use host pathways and appropriate them for their own benefit. .