Deglycosylation of human glycoconjugates by the sequential activities of exoglycosidases expressed by Streptococcus pneumoniae
Deglycosylation of human glycoconjugates by the sequential activities of exoglycosidases expressed by Streptococcus pneumoniae
复制标题
DOI：
10.1111/j.1365-2958.2005.04984.x
复制
发表时间：
2006-02-01
影响因子：
3.6
通讯作者：
Weiser, JN
中科院分区：
文献类型：
--
作者：
King, SJ;Hippe, KR;Weiser, JN
肺炎链球菌产生三种表面相关的外糖苷酶：神经氨酸酶NAA、β-半乳糖苷酶BGaA和β-N-乙酰氨基葡萄糖苷酶StrH。NANA去除末端唾液酸的拟议功能包括揭示黏附受体，影响糖基化宿主清除分子的功能，修改居住在相同生态位的其他细菌的表面，以及提供营养源。然而，尚不清楚肺炎链球菌是否能通过BgaA或StrH的活性进一步去糖化人类靶标。我们证明了NaNA、BgaA和StrH依次作用于去除唾液酸、半乳糖和N-乙酰氨基葡萄糖，并暴露在与肺炎球菌结合的人类糖蛋白上的甘露糖，从而保护呼吸道。此外，BGaA和NaNA都被证明有助于未被包裹的肺炎球菌与人类上皮细胞的黏附。尽管有这些发现，三重外切糖苷酶突变体在小鼠及其亲本菌株中定植，表明这些基因对定植和疾病的任何影响可能是宿主物种特有的。这些研究强调了考虑肺炎链球菌对人类靶标的完全脱糖能力的重要性，并表明除了NaA外，BgaA和StrH也有助于肺炎球菌的定植和/或致病。
Streptococcus pneumoniae produces three surface-associated exoglycosidases; a neuraminidase, NanA, a beta-galactosidase, BgaA, and a beta-N-acetylglucosaminidase, StrH. the proposed functions of NanA, which removes terminal sialic acid, include revealing receptors for adherence, affecting the function of glycosylated host clearance molecules, modifying the surface of other bacteria coinhabiting the same niche, and providing a nutrient source. However, it is unclear whether following desialylation S. pneumoniae can further deglycosylate human targets through the activity of BgaA or StrH. We demonstrate that NanA, BgaA and StrH act sequentially to remove sialic acid, galactose and N-acetylglucosamine and expose mannose on human glycoproteins that bind to the pneumococcus and protect the airway. In addition, both BgaA and NanA were shown to contribute to the adherence of unencapsulated pneumococci, to human epithelial cells. Despite these findings, triple exoglycosidase mutants colonized mice as well as their parental strains, suggesting that any effect of these genes on colonization and disease may be host species-specific. These studies highlight the importance of considering the complete ability of S. pneumoniae to deglycosylate human targets and suggest that in addition to NanA, BgaA and StrH also contribute to pneumococcal colonization and/or pathogenesis.