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Selective Inhibition of Sialic Acid-Based Molecular Mimicry in Haemophilus influenzae Abrogates Serum Resistance
Cell Chemical Biology ( IF 6.6 ) Pub Date : 2018-07-05 , DOI: 10.1016/j.chembiol.2018.05.018
Torben Heise , Jeroen D. Langereis , Emiel Rossing , Marien I. de Jonge , Gosse J. Adema , Christian Büll , Thomas J. Boltje

Pathogens such as non-typeableHaemophilus influenzae(NTHi) evade the immune system by presenting host-derived sialic acids. NTHi cannot synthesize sialic acids and therefore needs to utilize sialic acids originating from host tissue. Here we report sialic acid-based probes to visualize and inhibit the transfer of host sialic acids to NTHi. Inhibition of sialic acid utilization by NTHi enhanced serum-mediated killing. Furthermore, in anin vitromodel of the human respiratory tract, we demonstrate efficient inhibition of sialic acid transfer from primary human bronchial epithelial cells to NTHi using bioorthogonal chemistry.

中文翻译:

选择性抑制基于唾液酸的分子拟态在流感嗜血杆菌废品血清抗药性中的作用

诸如不可分型流感嗜血杆菌(NTHi)之类的病原体通过呈现宿主来源的唾液酸来逃避免疫系统。NTHi不能合成唾液酸,因此需要利用源自宿主组织的唾液酸。在这里,我们报告基于唾液酸的探针,以可视化并抑制宿主唾液酸向NTHi的转移。NTHi对唾液酸利用的抑制作用增强了血清介导的杀伤作用。此外,在人类呼吸道的体外模型中,我们证明了使用生物正交化学有效抑制唾液酸从原代人支气管上皮细胞向NTHi转移。
更新日期:2018-10-19
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