Knockouts of sulfur metabolism genes induce chronic inflammation and immune dysregulation in Drosophila melanogaster

Genetic disruptions in sulfur metabolism—specifically, combined deletions of the cbs, cse, and tst1 genes—lead to reduced H₂S levels and hyperhomocysteinemia in flies. These metabolic changes induce oxidative stress and trigger chronic inflammatory responses.

Transcriptomic analysis and q-PCR revealed significant activation of major immune pathways, including IMD, Toll, and Jac-Stat. A septic injection of Bacillus subtilis induces increased expression of antimicrobial peptides (AMPs) and pattern recognition receptors in knockout flies. Notably, double- and triple-knockout strains exhibit prolonged immune activation.