Anthrax lethal factor and edema factor act on conserved targets in Drosophila.

摘要: Many bacterial toxins act on conserved components of essential host-signaling pathways. One consequence this conservation is that genetic model organisms such as Drosophila melanogaster can be used for analyzing the mechanism toxin action. In study, we characterize activities two anthrax virulence factors, lethal factor (LF) and edema factor, in transgenic Drosophila. LF a zinc metalloprotease cleaves inactivates most human mitogen-activated protein kinase (MAPK) kinases (MAPKKs). We found similarly MAPK Hemipterous (Hep) Licorne vitro. Consistent with these observations, expression inhibited Hep/c-Jun N-terminal pathway during embryonic dorsal closure related process adult thoracic closure. Epistasis experiments confirmed acts at level Hep. also inhibits Ras/MAPK signaling wing development upstream downstream Raf, consistent acting Dsor. addition, potent adenylate cyclase, hh development, known role cAMP-dependent PKA suppressing Hedgehog response. These results demonstrate function they do mammalian cells open way to using multicellular host system studying vivo diverse factors.