Editors' ChoiceHost-Pathogen Interactions

Venomous SERCA

Science Signaling  11 Jun 2013:
Vol. 6, Issue 279, pp. ec133
DOI: 10.1126/scisignal.2004409

Parasitoid wasps are a natural pathogen for fruit flies, injecting venom and an egg into fly larvae. Flies mount an immune response that involves the activation of plasmatocytes and lamellocytes, which encapsulate the injected wasp egg, ultimately killing the developing wasp. Pathogenic, virulent wasps have mechanisms to escape this response. Mortimer et al. identified a mechanism involving inhibition of calcium signaling that contributed to the virulence of Ganaspis sp. 1 (G1) for Drosophila melanogaster. G1 successfully parasitized multiple fruit fly species, including D. melanogaster. G1 attack of larvae also rescued a self-encapsulation phenotype of a specific D. melanogaster mutant, suggesting that G1 could suppress the fly immune response. However, G1 attack of larvae stimulated an increase in hemocytes and lamellocytes, suggesting that the compromised immune response was not resulting from cell death. Through a combination of proteomics and transcriptomics, a protein with homology to sarcoplasmic and endoplasmic reticulum Ca2+ ATPases (SERCA) was identified as an abundant venom protein. This venom SERCA was a short isoform, SERCA1002. Plasmatocytes expressing a genetically encoded calcium sensor that were exposed to fly venom showed reduced calcium signaling, and this effect was blocked by preincubation of the venom with the SERCA inhibitor thapsigargin. Similarly, calcium signaling in larvae attacked by G1 was reduced compared with that in larvae attacked by an avirulent wasp species. Expression of a calcium-binding protein that inhibits calcium signaling compromised the encapsulation of the normally avirulent wasp eggs. Knockdown of the fly ryanodine receptor homolog, but not the inositol 1,4,5-trisphosphate receptor homolog, also compromised encapsulation of the normally avirulent wasp eggs. Mutant flies with increased intracellular calcium concentrations exhibited enhanced encapsulation of the G1 eggs, but encapsulation of eggs of another wasp that does not have SERCA in its venom was unaffected. How this large, transmembrane protein accumulates in venom and is delivered to the host remains an open question, but clearly interfering with the fly immune cell calcium signaling response is an effective strategy for wasp virulence.

N. T. Mortimer, J. Goecks, B. Z. Kacsoh, J. A. Mobley, G. J. Bowersock, J. Taylor, T. A. Schlenke, Parasitoid wasp venom SERCA regulates Drosophila calcium levels and inhibits cellular immunity. Proc. Natl. Acad. Sci. U.S.A. 110, 9427–9432 (2013). [Abstract] [Full Text]