Identification and characterization of differentially expressed genes inCaenorhabditis elegansin response to pathogenic and nonpathogenicStenotrophomonas maltophilia

Background Stenotrophomonas maltophiliais an emerging nosocomial pathogen that causes infection in immunocompromised patients.S. maltophiliaisolates are genetically diverse, contain diverse virulence factors, and are variably pathogenic within several host species. Members of theStenotrophomonasgenus are part of the native microbiome ofC. elegans, being found in greater relative abundance within the worm than its environment, suggesting that these bacteria accumulate withinC. elegans. Thus, study of theC. elegans-Stenotrophomonasinteraction is of both medical and ecological significance. To identify host defense mechanisms, we analyzed theC. eleganstranscriptomic response toS. maltophiliastrains of varying pathogenicity: K279a, an avirulent clinical isolate, JCMS, a virulent strain isolated in association with soil nematodes near Manhattan, KS, and JV3, an even more virulent environmental isolate. Results Overall, we found 145 genes that are commonly differentially expressed in response to pathogenicS. maltophiliastrains, 89% of which are upregulated, with many even further upregulated in response to JV3 as compared to JCMS. There are many more JV3-specific differentially expressed genes (225, 11% upregulated) than JCMS-specific differentially expressed genes (14, 86% upregulated), suggesting JV3 has unique pathogenic mechanisms that could explain its increased virulence. We used connectivity within a gene network model to choose pathogen-specific and strain-specific differentially expressed candidate genes for functional analysis. Mutations in 13 of 22 candidate genes caused significant differences inC. eleganssurvival in response to at least oneS. maltophiliastrain, although not always the strain that induced differential expression, suggesting a dynamic response to varying levels of pathogenicity. Conclusions Variation in observed pathogenicity and differences in host transcriptional responses toS. maltophiliastrains reveal that strain-specific mechanisms play important roles inS. maltophiliapathogenesis. Furthermore, utilizing bacteria closely related to strains found inC. elegansnatural environment provides a more realistic interaction for understanding host-pathogen response.