The bacterivorous nematode Caenorhabditis elegans is an excellent model to study host innate immune responses to various bacterial pathogens, including the emerging nosocomial pathogen Stenotrophomonas maltophilia. Members of the Stenotrophomonas genus are components of the C. elegans natural habitat and native microbiome (Dirksen et al., 2016; Samuel et al., 2017). Thus, the study of this interaction has both medical and ecological relevance. We have previously shown that many of the C. elegans conserved innate immune pathways function to protect the nematode from S. maltophilia isolates (White et al., 2016). However, S. maltophilia strains JCMS and JV3 are virulent to normally pathogen-resistant
daf-2 mutants. This suggests that pathogenic stains of S. maltophilia evade the pathogen resistance conferred by activation of the DAF-2/16 pathway. In an effort to understand how pathogenic S. maltophilia JCMS and JV3 are able to bypass the nematode's DAF-2/16 pathway defenses, we used transcriptional profiling in wild-type and
daf-2 mutants to identify candidate C. elegans innate immunity genes that may be targeted by S. maltophilia to defeat host defenses. To this end, we have identified 88 genes that are significantly differentially expressed in the absence of
daf-2 function upon exposure to pathogenic S. maltophilia. We hypothesize that pathogenic S. maltophilia may block the function of expressed genes and candidate target genes will be contained within this subset. We also hypothesize that S. maltophilia may prevent the expression of genes and such candidate target genes will not be contained within this subset of differentially expressed genes. Regardless of the S. maltophilia mechanism of pathogenicity, we hypothesize that candidate target genes will be differentially expressed in response to other pathogens that are susceptible to DAF-2/16 pathway defenses and regulated by the DAF-16 transcription factor. These candidate gene criteria were used in conjunction with connectivity within a gene network model and mutant allele availability to select candidate target genes for functional analyses. We expect that candidate S. maltophilia target genes should be required for
daf-2-mediated lifespan extension and are using RNA interference to test this prediction. Future characterization of these candidate target genes may help us elucidate the underlying mechanisms that enable pathogenic S. maltophilia to defeat the nematode's innate immune responses.