A Comprehensive Analysis of Gene Expression Changes Provoked by Bacterial and Fungal Infection in C. elegans

Abstract

While Caenorhabditis elegans specifically responds to infection by the up-regulation of certain genes, distinct pathogens trigger the expression of a common set of genes. We applied new methods to conduct a comprehensive and comparative study of the transcriptional response of C. elegans to bacterial and fungal infection. Using tiling arrays and/or RNA-sequencing, we have characterized the genome-wide transcriptional changes that underlie the host's response to infection by three bacterial (Serratia marcescens, Enterococcus faecalis and otorhabdus luminescens) and two fungal pathogens (Drechmeria coniospora and Harposporium sp.). We developed a flexible tool, the WormBase Converter (available at http://wormbasemanager.sourceforge.net/), to allow cross-study comparisons. The new data sets provided more extensive lists of differentially regulated genes than previous studies. Annotation analysis confirmed that genes commonly up-regulated by bacterial infections are related to stress responses. We found substantial overlaps between the genes regulated upon intestinal infection by the bacterial pathogens and Harposporium, and between those regulated by Harposporium and D. coniospora, which infects the epidermis. Among the fungus-regulated genes, there was a significant bias towards genes that are evolving rapidly and potentially encode small proteins. The results obtained using new methods reveal that the response to infection in C. elegans is determined by the nature of the pathogen, the site of infection and the physiological imbalance provoked by infection. They form the basis for future functional dissection of innate immune signaling. Finally, we also propose alternative methods to identify differentially regulated genes that take into account the greater variability in lowly expressed genes.

Antimicrobial effectors in the nematode Caenorhabditis elegans : an outgroup to the Arthropoda

“…For this analysis and also all further assessments below, we considered a total of 111 differentially expressed gene sets from 35 transcriptome studies, which examined the C. elegans response to bacteria, fungi and one virus at various exposure time periods (electronic supplementary material, table S1). This confirms previous observations [50] and supports the role of NLP and CNC peptides as inducible anti-fungal effectors. One exception is infection with the Gram-positive bacterium Xenorhabdus nematophila, which induces the expression of several cnc and nlp genes (figure 2).…”

“…fungus versus bacterium) and site of infection (i.e. intestine versus epidermis) can influence effector gene expression in the worm [50].…”

“…These genes are induced in expression upon infection with fungal pathogens such as D. coniospora or Harposporium sp. [50]. Caenorhabditis elegans possesses seven fip genes and 29 fipr genes which generally vary in their expression upon pathogen exposure (electronic supplementary material, figures S1 and S2).…”

The Mediator Kinase Module Restrains Epidermal Growth Factor Receptor Signaling and Represses Vulval Cell Fate Specification in Caenorhabditis elegans

“…We found that 829 genes were upregulated and 461 genes were downregulated more than twofold in cdk-8 null mutants, representing 6.7% of all C. elegans genes (Table S1). To identify cdk-8-dependent gene programs, we compared our lists of cdk-8 regulated genes to other gene lists using EASE (Hosack et al 2003;Engelmann et al 2011). The top hit among genes upregulated in cdk-8 mutants was a set of genes upregulated in lin-35/Retinoblastoma (RB) synMuv gene mutants (Kirienko and Fay 2007), and lin-35-repressed genes also overlapped significantly with genes downregulated in cdk-8 mutants (Figure 2A).…”

Epidermal Wound Healing in the Nematode Caenorhabditis elegans

“…25,26 The signal transduction pathways responsible for induction of AMP expression in response to infection have been extensively characterized and reviewed recently. 27,28 In overview, at least two major pathways regulate epidermal AMP induction: a MAPK cascade required for induction of the neuropeptide-like (nlp) genes 23 ( Fig.…”