The peptidoglycan recognition protein PGRP-SC1a is essential for toll signaling and phagocytosis of Staphylocloccus aureus in Drosophila
The peptidoglycan recognition protein PGRP-SC1a is essential for toll signaling and phagocytosis of Staphylocloccus aureus in Drosophila
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DOI：
10.1073/pnas.0506182103
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发表时间：
2006-01-17
影响因子：
11.1
通讯作者：
Wu, LP
中科院分区：
文献类型：
--
作者：
Garver, LS;Wu, JL;Wu, LP
从果蝇吞噬突变体的正向遗传筛选中，我们确定了一个突变，影响肽聚糖识别蛋白（PGRP）SC 1a和削弱吞噬细菌金黄色葡萄球菌的能力，但不是大肠杆菌和枯草芽孢杆菌。由于这些细菌中肽聚糖肽键的差异，我们的数据表明PGRP-SC 1a对于识别大多数革兰氏阳性细菌典型的Lys型肽聚糖是必需的。PGRP-SC 1 a突变体也不能激活Toll/NF-κ B信号通路，并且在S.金黄色葡萄球菌感染。这种突变表型是首次发现的N-乙酰胞壁酰-L-丙氨酸酰胺酶PGRP，其在聚糖骨架和交联茎肽之间的乳酰酰胺键处切割肽聚糖。通过产生表达野生型或非催化性半胱氨酸-丝氨酸突变体PGRP-SC 1a的转基因救援果蝇，我们发现PGRP-SC 1a酰胺酶活性对于Toll信号传导不是必需的，但是对于S.金黄色葡萄球菌进入宿主吞噬细胞和生存后，金黄色葡萄球菌感染。此外，我们发现PGRP-SC 1a酰胺酶活性可以通过外源性添加游离肽聚糖来取代，这表明肽聚糖切割产物的存在比细菌表面上产生切割的肽聚糖对PGRP-SC 1a介导的吞噬作用更重要。
From a forward genetic screen for phagocytosis mutants in Drosophila melanogaster, we identified a mutation that affects peptidoglycan recognition protein (PGRP) SC1a and impairs the ability to phagocytose the bacteria Staphylococcus aureus, but not Escherichia coli and Bacillus subtilis. Because of the differences in peptidoglycan peptide linkages in these bacteria, our data suggest that PGRP-SC1a is necessary for recognition of the Lys-type peptidoglycan typical of most Gram(+) bacteria. PGRP-SC1a mutants also fail to activate the Toll/NF-kappa B signaling pathway and are compromised for survival after S. aureus infection. This mutant phenotype is the first found for an N-acetylmuramoyl-L-alanine amidase PGRP that cleaves peptidoglycan at the lactylamide bond between the glycan backbone and the crosslinking stem peptides. By generating transgenic rescue flies that express either wild-type or a noncatalytic cysteine-serine mutant PGRP-SC1a, we find that PGRP-SC1a amidase activity is not necessary for Toll signaling, but is essential for uptake of S. aureus into the host phagocytes and for survival after S. aureus infection. Furthermore, we find that the PGRP-SC1a amidase activity can be substituted by exogenous addition of free peptidoglycan, suggesting that the presence of peptidoglycan cleavage products is more important than the generation of cleaved peptidoglycan on the bacterial surface for PGRP-SC1a mediated phagocytosis.