The Jun Homolog Jra Mediates Toxin Response In Drosophila Melanogaster.

Abstract

Insects that ingest microbial pathogens are also exposed to their toxins. The sensitivity of insects to ingested toxins of human pathogens and the potential mechanism of toxin resistance has not been thoroughly studied. We tested the survival of Drosophila melanogaster orally fed with exotoxins and endotoxins of ten human bacterial pathogens. We discovered that only a few toxins adversely affect fly survival, and that most toxins either do not affect or paradoxically extend insect survival (hormetic effect) at the dosages tested. We found that in Drosophila, Jra, a homolog of stress response transcription factor Jun, mediates a broad-spectrum toxin response, since the survival of Jra mutants was shortened in the presence of most of the tested toxins. This study begins to uncover the mechanism of the response of insects to toxins. It describes how a toxin-induced Jun stress response system helps insects reduce their sensitivity to toxins of human pathogens. Keywords: toxin; sensitivity; resistance; survival; immunity; Drosophila melanogaster Abbreviations: Jun related antigen (Jra); immune deficiency (Imd); antimicrobial peptides (AMP); mitogen-activated protein kinase (MAPK); Bloomington Drosophila stock center (BDSC); wild type (WT); lipopolysaccharide (LPS); adenosine diphosphate (ADP); adenosine triphosphate (ATP); adenosine monophosphate (cAMP); Jun N-terminal Kinase (JNK); Nuclear Factor-κB (NF-κB); absorption, distribution, metabolism, and excretion (ADME); absorption, distribution, metabolism, excretion, and toxicity (ADMET); confidence interval (CI); soluble N-ethylmale-imide-sensitive factorattachment protein receptors (SNARE); basic leucine zipper (bZIP); deoxyribonucleic acid (DNA); eukaryotic elongation factor (eEF); programmed death-ligand (PD-L); cluster of differentiation (CD).