The saposin-like protein SPP-12 is an antimicrobial polypeptide in the pharyngeal neurons of Caenorhabditis elegans and participates in defence against a natural bacterial pathogen.

Caenopores are antimicrobial and pore-forming polypeptides in Caenorhabditis elegans belonging to the saposin-like protein superfamily and are considered important elements of the nematode's intestinal immune system. In the present study, we demonstrate that, unlike the other members of the multifarious gene family (spps) coding for caenopores, spp-12 is expressed exclusively in two pharyngeal neurons. Recombinantly expressed SPP-12 binds to phospholipid membranes and forms pores in a pH-dependent manner characteristic of caenopores. Moreover, SPP-12 kills viable Gram-positive bacteria, yeast cells and amoebae by permeabilizing their membranes, suggesting a wide-target cell spectrum. A spp-12 knockout mutant is more susceptible to pathogenic Bacillus thuringiensis than wild-type worms and is tolerant to non-pathogenic bacteria. By contrast, SPP-1, a caenopore, whose gene is expressed only in the intestine and reported to be regulated by the same pathway as spp-12, is apparently non-protective against pathogenic B. thuringiensis, although it also does display antimicrobial activity. The transcription of spp-1 is down-regulated in wild-type worms in the presence of pathogenic B. thuringiensis and a spp-1 knockout mutant is hyposusceptible to this bacterium. This implies that SPP-12, but not SPP-1, contributes to resistance against B. thuringiensis, a natural pathogen of the nematode.