Sensing of Gram-positive bacteria in Drosophila: GNBP1 is needed to process and present peptidoglycan to PGRP-SA

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Abstract
Genetic evidence indicates that Drosophila defense against Gram‐positive bacteria is mediated by two putative pattern recognition receptors acting upstream of Toll, namely Gram‐negative binding protein 1 (GNBP1) and peptidoglycan recognition protein SA (PGRP‐SA). Until now however, the molecular recognition proceedings for sensing of Gram‐positive pathogens were not known. In the present, we report the physical interaction between GNBP1 and PGRP‐SA using recombinant proteins. GNBP1 was able to hydrolyze Gram‐positive peptidoglycan (PG), while PGRP‐SA bound highly purified PG fragments (muropeptides). Interaction between these proteins was enhanced in the presence of PG or muropeptides. PGRP‐SA binding depended on the polymerization status of the muropeptides, pointing to constraints in the number of PGRP‐SA molecules bound for signaling initiation. We propose a model whereby GNBP1 presents a processed form of PG for sensing by PGRP‐SA and that a tripartite interaction between these proteins and PG is essential for downstream signaling.