Endosulfatases SULF1 and SULF2 limit Chlamydia muridarum infection.
Endosulfatases SULF1 and SULF2 limit Chlamydia muridarum infection.
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DOI：
10.1111/cmi.12133
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发表时间：
2013-09
影响因子：
3.4
通讯作者：
Engel JN
中科院分区：
文献类型：
--
作者：
Kim JH;Chan C;Elwell C;Singer MS;Dierks T;Lemjabbar-Alaoui H;Rosen SD;Engel JN
衣原体附着于宿主细胞的第一步被认为涉及与宿主硫酸乙酰肝素蛋白聚糖（HSPG）的可逆结合，HSPG是与不同蛋白质骨架偶联的硫酸乙酰肝素重复二糖单元的聚合物。然而，参与衣原体结合的HSPG结构的关键决定因素并不完全确定。先前的全基因组果蝇RNAi筛选表明，HSPG 6-O硫酸化水平而不是蛋白聚糖骨架的身份可能是结合的关键决定因素。在这里，我们在哺乳动物细胞中测试了SULF 1或SULF 2，即从HSPG中去除6-O硫酸盐的人内硫酸酯酶，是否调节衣原体感染。SULF 1或SULF 2在HeLa细胞中的异位表达，减少了细胞表面HSPG硫酸化，减少了C。mudarum结合和减少空泡形成。在主要表达SULF 2的细胞系中内源性SULF 2的shRNA消耗增强了结合并增加了空泡形成。C.不同细胞系的鼠伤寒沙门氏菌感染导致SULF 2 mRNA的下调。在急性肺炎的小鼠模型中，两种内硫酸酯酶基因缺陷或仅SULF 2基因缺陷的小鼠表现出对C.鼠肺感染总的来说，这些研究表明，HSPG 6-O硫酸化水平是C。在体内的muridarum感染和6-O endosulfatases是以前不受重视的微生物发病机制的调节剂。
The first step in attachment of Chlamydia to host cells is thought to involve reversible binding to host heparan sulfate proteoglycans (HSPGs), polymers of variably sulfated repeating disaccharide units coupled to diverse protein backbones. However, the key determinants of HSPG structure that are involved in Chlamydia binding are incompletely defined. A previous genome-wide Drosophila RNAi screen suggested that the level of HSPG 6-O sulfation rather than the identity of the proteoglycan backbone maybe a critical determinant for binding. Here, we tested in mammalian cells whether SULF1 or SULF2, human endosulfatases which remove 6-O sulfates from HSPGs, modulate Chlamydia infection. Ectopic expression of SULF1 or SULF2 in HeLa cells, which decreases cell surface HSPG sulfation, diminished C. muridarum binding and decreased vacuole formation. ShRNA depletion of endogenous SULF2 in a cell line that primarily expresses SULF2 augmented binding and increased vacuole formation. C. muridarum infection of diverse cell lines resulted in downregulation of SULF2 mRNA. In a murine model of acute pneumonia, mice genetically deficient in both endosulfatases or in SULF2 alone demonstrated increased susceptibility to C. muridarum lung infection. Collectively, these studies demonstrate that the level of HSPG 6-O sulfation is a critical determinant of C. muridarum infection in vivo and that 6-O endosulfatases are previously unappreciated modulators of microbial pathogenesis.
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影响因子：
11.2
作者：
Chau, B. Nelson;Diaz, Robert L.;Cleary, Michele A.
通讯作者：
Cleary, Michele A.
影响因子：
3.1
作者：
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通讯作者：
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影响因子：
13.5
作者：
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通讯作者：
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影响因子：
6.7
作者：
Elwell, Cherilyn A.;Ceesay, Alhaji;Kim, Jung Hwa;Kalman, Daniel;Engel, Joanne N.
通讯作者：
Engel, Joanne N.
影响因子：
37.3
作者：
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通讯作者：
Friess H