title: Requirements of peptidoglycan structure that allow detection by the Drosophila Toll pathway.
abstract: The Drosophila immune system is able to discriminate between classes of bacteria. Detection of Gram-positive bacteria involves a complex of two pattern recognition receptors: peptidoglycan recognition protein SA (PGRP-SA) and Gram-negative binding protein 1 (GNBP1). These activate the Toll signalling pathway. To define the cell wall components sensed by the host, we used highly purified peptidoglycan fragments of two principal Gram-positive bacterial pathogens Staphylococcus aureus and Streptococcus pneumoniae. We report that in both peptidoglycans, the minimal structure needed to activate the Toll pathway is a muropeptide dimer and that the free reducing end of the N-acetyl muramic acid residues of the muropeptides is essential for activity. Monomeric muropeptides were inactive and inhibitory in combination with dimers. Finally, peptidoglycan was degraded by the haemolymph of wild-type but not GNBP1 mutant flies. We suggest a model whereby GNBP1 is involved in the hydrolysis of Gram-positive peptidoglycan producing new glycan reducing ends, which are subsequently detected by PGRP-SA.
authors.affiliation: Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
authors.forename: Sergio R
authors.initials: SR
authors.lastname: Filipe
authors.forename: Alexander
authors.initials: A
authors.lastname: Tomasz
authors.forename: Petros
authors.initials: P
authors.lastname: Ligoxygakis
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002473:Cell Wall / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004330:Drosophila / Q000378:metabolism* / Q000502:physiology; D029721:Drosophila Proteins / Q000378:metabolism*; D006458:Hemolymph / Q000378:metabolism; D008954:Models, Biological; D009112:Muramic Acids / Q000378:metabolism; D010457:Peptidoglycan / Q000737:chemistry* / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013211:Staphylococcus aureus / Q000737:chemistry; D013296:Streptococcus pneumoniae / Q000737:chemistry; D051193:Toll-Like Receptors
chemical_list: D002352:Carrier Proteins; D029721:Drosophila Proteins; C480085:Gnbp1 protein, Drosophila; D009112:Muramic Acids; D010457:Peptidoglycan; D011956:Receptors, Cell Surface; C068721:Tl protein, Drosophila; D051193:Toll-Like Receptors; C118897:peptidoglycan recognition protein