During
group B streptococcal infection, the alpha C
protein (ACP) on the bacterial surface binds to host cell surface
heparan sulfate proteoglycans (HSPGs) and facilitates entry of bacteria into human epithelial cells. Previous studies in a Drosophila melanogaster model showed that binding of ACP to the sulfated
polysaccharide chains (
glycosaminoglycans) of HSPGs promotes host death and is associated with higher bacterial burdens. We hypothesized that ACP-
glycosaminoglycan binding might determine
infection outcome by altering host responses to
infection, such as expression of
antimicrobial peptides. As
glycosaminoglycans/HSPGs also interact with a number of endogenous secreted signaling molecules in Drosophila, we examined the effects of host and pathogen
glycosaminoglycan/
HSPG-binding structures in host survival of
infection and
antimicrobial peptide expression. Strikingly, host survival after
infection with wild-type streptococci was enhanced among flies overexpressing the endogenous
glycosaminoglycan/
HSPG-binding morphogen Decapentaplegic-a
transforming growth factor β-like Drosophila homolog of mammalian
bone morphogenetic proteins-but not by flies overexpressing a mutant, non-
glycosaminoglycan-binding Decapentaplegic, or the other endogenous
glycosaminoglycan/
HSPG-binding morphogens, Hedgehog and Wingless. While ACP-
glycosaminoglycan binding was associated with enhanced transcription of
peptidoglycan recognition proteins and
antimicrobial peptides, Decapentaplegic overexpression suppressed transcription of these genes during
streptococcal infection. Further, the
glycosaminoglycan-binding domain of ACP competed with Decapentaplegic for binding to the soluble
glycosaminoglycan heparin in an in vitro assay. These data suggest that, in addition to promoting bacterial entry into host cells, ACP competes with Decapentaplegic for binding to
glycosaminoglycans/HSPGs during
infection and that these bacterial and endogenous
glycosaminoglycan-binding structures determine host survival and regulate
antimicrobial peptide transcription.