Genetic and Physiological Activation of Osmosensitive Gene Expression Mimics Transcriptional Signatures of Pathogen Infection in C. elegans

Abstract

The soil-dwelling nematode C. elegans is a powerful system for comparative molecular analyses of environmental stress response mechanisms. Infection of worms with bacterial and fungal pathogens causes the activation of well-characterized innate immune transcriptional programs in pathogen-exposed hypodermal and intestinal tissues. However, the pathophysiological events that drive such transcriptional responses are not understood. Here, we show that infection-activated transcriptional responses are, in large part, recapitulated by either physiological or genetic activation of the osmotic stress response. Microarray profiling of wild type worms exposed to non-lethal hypertonicity identified a suite of genes that were also regulated by infection. Expression profiles of five different osmotic stress resistant (osr) mutants under isotonic conditions reiterated the wild type transcriptional response to osmotic stress and also showed substantial similarity to infection-induced gene expression under isotonic conditions. Computational, transgenic, and functional approaches revealed that two GATA transcription factors previously implicated in infection-induced transcriptional responses, elt-2 and elt-3, are also essential for coordinated tissue-specific activation of osmosensitive gene expression and promote survival under osmotically stressful conditions. Together, our data suggest infection and osmotic adaptation share previously unappreciated transcriptional similarities which might be controlled via regulation of tissue-specific GATA transcription factors.

Physiological and molecular mechanisms of salt and water homeostasis in the nematodeCaenorhabditis elegans

“…1C). Whole genome cDNA microarray studies have confirmed that, in addition to gpdh-1, mutations in osr-1, osm-7, osm-8, and osm-11 constitutively activate many genes that are responsive to high osmolarity, indicating that they mimic signaling changes that normally occur with high osmolarity (99).…”

“…A major remaining question is the identity of the inducible transcription factor that transactivates gpdh-1 and other osmosensitive genes (99). In many mammalian cells, the rel-type transcription factor NFAT5/TonEBP accumulates in the nucleus in response to high osmolarity and orchestrates adaptive gene expression (81).…”

“…C. elegans does not have a close homolog of this or other rel-type factors. Bioinformatic analysis determined that GATA transcription binding sites are enriched in the regulatory sequences of osmosensitive genes (99). Furthermore, putative GATA binding sites and two GATA factors, elt-2 and elt-3, were shown to be required for activation of the gpdh-1 promoter by high osmolarity and osm-7 and osm-11 mutations.…”

“…Many HSP genes are also induced by other types of stress (117). However, C. elegans does not activate canonical HSPs during hypertonic stress (99). Alternatively, it was reported that acclimation to hypertonicity strongly and constitutively decreased synthesis of new proteins without increasing the rate of protein degradation (14).…”

Glycogen: A must have storage to survive stressful emergencies

“…[5][6][7] Importantly, several hyperosmotic stressresistant C. elegans mutants display heightened glycerol levels due to constitutive activation of gpdh-1 and subsequent glycerol accumulation. [8][9][10][11][12] Although the use of glycerol in invertebrates to survive hyperosmotic stress is widely accepted, what fuels the rapid glycerol production upon hyperosmotic stress exposure has not been clearly elucidated.…”