Myc Mediates Toxin Response in Female Drosophila melanogaster.

Flies naturally contain microbes in their intestines after eating microbe-rich food like decaying fruits. When ingesting microbes, insects are also exposed to their toxins. The sensitivity of insects to ingested microbial toxins and their mechanism of response to toxins has not been thoroughly studied. Transcriptional regulator c-Myc has been shown to regulate the response to some but not all microbial toxins in mammals. We tested the sensitivity of wild-type and Myc mutant Drosophila melanogaster strains to two exotoxins, Clostridium perfringens α-toxin and Vibrio cholerae toxin, and two endotoxins, lipopolysaccharides (LPS) of Salmonella minnesota and S. typhimurium. We observed that both sexes of wild-type flies were insensitive to tested toxins. Similarly, Myc mutant males were insensitive to the four toxins. In contrast, female Myc mutants were significantly more sensitive to all tested toxins than wild-type females. The median survival of female Myc mutants was shortened by at least 54 hours in the presence of bacterial toxins. The component of LPS, lipid A, shortened the median survival of Myc females by 104 hours, indicating that the toxicity of LPS is caused by lipid A. This study demonstrates a sex-specific mechanism of the response of insects to toxins and describes that Myc protects female fruit flies from the tested microbial toxins. Keywords: bacterial toxins; sensitivity; resistance; survival; immunity; Drosophila melanogaster Abbreviations: Immune deficiency (Imd); antimicrobial peptides (AMP); mitogen-activated protein kinase (MAPK); Bloomington Drosophila stock center (BDSC); wild type (WT); lipopolysaccharide (LPS); adenosine diphosphate (ADP); 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); deoxyribonucleic acid (DNA); intestinal stem cells (ISCs); Janus kinases (JAK); signal transducer and activator of transcription (STAT); epidermal growth factor EGF; and Wingless (Wg).