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The bacterivorous nematode  Caenorhabditis elegans  is an excellent model for the study of innate immune responses to a variety of bacterial pathogens, including the emerging nosocomial bacterial pathogen  Stenotrophomonas maltophilia . The study of this interaction has ecological and medical relevance as  S. maltophilia  is found in association with  C. elegans  and other nematodes in the wild and is an emerging opportunistic bacterial pathogen. We identified 393 genes that were differentially expressed when exposed to virulent and avirulent strains of  S. maltophilia  and an avirulent strain of  E. coli . We then used a probabilistic functional gene network model (WormNet) to determine that 118 of the 393 differentially expressed genes formed an interacting network and identified a set of highly connected genes with eight or more predicted interactions. We hypothesized that these highly connected genes might play an important role in the defense against  S. maltophila  and found that mutations of six of seven highly connected genes have a significant effect on nematode survival in response to these bacteria. Of these genes, C48B4.1,  mpk-2, cpr-4, clec-67 , and  lys-6  are needed for combating the virulent  S. maltophilia  JCMS strain, while  dod-22  was solely involved in response to the avirulent  S. maltophilia  K279a strain. We further found that  dod-22  and  clec-67  were up regulated in response to JCMS vs. K279a, while C48B4.1,  mpk-2, cpr-4 , and  lys-6  were down regulated. Only  dod-22  had a documented role in innate immunity, which demonstrates the merit of our approach in the identification of novel genes that are involved in combating  S. maltophilia  infection.

frontiers in cellular and infection microbiology

Transcriptomic, Functional, and Network Analyses Reveal Novel Genes Involved in the Interaction Between Caenorhabditis elegans and Stenotrophomonas maltophilia