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首页> 外文期刊>Infection and immunity >Host Glycosaminoglycan Confers Susceptibility to Bacterial Infection in Drosophila melanogaster
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Host Glycosaminoglycan Confers Susceptibility to Bacterial Infection in Drosophila melanogaster

机译：宿主糖胺聚糖赋予果蝇果蝇细菌感染的易感性

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Many pathogens engage host cell surface glycosaminoglycans, but redundancy in pathogen adhesins and host glycosaminoglycan-anchoring proteins (heparan sulfate proteoglycans) has limited the understanding of the importance of glycosaminoglycan binding during infection. The alpha C protein of group B streptococcus, a virulence determinant for this neonatal human pathogen, binds to host glycosaminoglycan and mediates the entry of bacteria into human cells. We studied alpha C protein-glycosaminoglycan binding in Drosophila melanogaster, whose glycosaminoglycan repertoire resembles that of humans but whose genome includes only three characterized membrane heparan sulfate proteoglycan genes. The knockdown of glycosaminoglycan polymerases or of heparan sulfate proteoglycans reduced the cellular binding of alpha C protein. The interruption of alpha C protein-glycosaminoglycan binding was associated with longer host survival and a lower bacterial burden. These data indicate that the glycosaminoglycan-alpha C protein interaction involves multiple heparan sulfate proteoglycans and impairs bacterial killing. Host glycosaminoglycans, anchored by multiple proteoglycans, thereby determine susceptibility to infection. Because there is homology between Drosophila and human glycosaminoglycan/proteoglycan structures and many pathogens express glycosaminoglycan-binding structures, our data suggest that interfering with glycosaminoglycan binding may protect against infections in humans.
机译：许多病原体与宿主细胞表面的糖胺聚糖结合，但是病原体粘附素和宿主糖胺聚糖锚定蛋白（硫酸乙酰肝素蛋白聚糖）的冗余性限制了对感染期间糖胺聚糖结合重要性的理解。 B族链球菌的αC蛋白是这种新生人类病原体的毒性决定因素，它与宿主糖胺聚糖结合并介导细菌进入人细胞。我们研究了果蝇（Drosophila melanogaster）中的αC蛋白-糖胺聚糖结合，该蛋白的糖胺聚糖类与人相似，但其基因组仅包含三个特征性的膜硫酸乙酰肝素蛋白聚糖基因。糖胺聚糖聚合酶或硫酸乙酰肝素蛋白聚糖的敲低减少了αC蛋白的细胞结合。 αC蛋白-糖胺聚糖结合的中断与更长的宿主存活和更低的细菌负担有关。这些数据表明糖胺聚糖-αC蛋白相互作用涉及多个硫酸乙酰肝素蛋白聚糖，并损害​​细菌的杀伤力。宿主糖胺聚糖，由多种蛋白聚糖锚定，从而确定对感染的敏感性。由于果蝇与人糖胺聚糖/蛋白聚糖结构之间存在同源性，并且许多病原体表达糖胺聚糖结合结构，因此我们的数据表明，干扰糖胺聚糖结合可以预防人类感染。

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