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Sialylation of Lipooligosaccharides Promotes Biofilm Formation by Nontypeable Haemophilus influenzae

机译:脂寡糖的唾液酸化促进不可分型流感嗜血杆菌的生物膜形成。

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Nontypeable Haemophilus influenzae (NTHi) is a major cause of opportunistic respiratory tract infections, including otitis media and bronchitis. The persistence of NTHi in vivo is thought to involve bacterial persistence in a biofilm community. Therefore, there is a need for further definition of bacterial factors contributing to biofilm formation by NTHi. Like other bacteria inhabiting host mucosal surfaces, NTHi has on its surface a diverse array of lipooligosaccharides (LOS) that influence host-bacterial interactions. In this study, we show that LOS containing sialic (N-acetyl-neuraminic) acid promotes biofilm formation by NTHi in vitro and bacterial persistence within the middle ear or lung in vivo. LOS from NTHi in biofilms was sialylated, as determined by comparison of electrophoretic mobilities and immunochemical reactivities before and after neuraminidase treatment. Biofilm formation was significantly reduced in media lacking sialic acid, and a siaB (CMP-sialic acid synthetase) mutant was deficient in biofilm formation in three different in vitro model systems. The persistence of an asialylated siaB mutant was attenuated in a gerbil middle ear infection model system, as well as in a rat pulmonary challenge model system. These data show that sialylated LOS glycoforms promote biofilm formation by NTHi and persistence in vivo.
机译:非典型性流感嗜血杆菌(NTHi)是机会性呼吸道感染的主要原因,包括中耳炎和支气管炎。 NTHi在体内的持久性被认为与生物膜群落中细菌的持久性有关。因此,需要进一步定义有助于NTHi形成生物膜的细菌因子。像其他居住在宿主粘膜表面的细菌一样,NTHi在其表面上也存在各种各样的脂寡糖(LOS),它们会影响宿主与细菌的相互作用。在这项研究中,我们表明,含有唾液酸( N -乙酰神经氨酸)的LOS可以促进NTHi体外生物膜的形成以及体内中耳或肺中细菌的持久性。通过比较神经氨酸酶处理前后的电泳迁移率和免疫化学反应性,确定了生物膜中NTHi的LOS被唾液酸化。在缺少唾液酸的培养基中,生物膜形成显着减少,并且在三个不同的体外模型系统中, siaB (CMP-唾液酸合成酶)突变体在生物膜形成方面均缺乏。沙化的 siaB 突变体的持久性在沙鼠中耳感染模型系统以及大鼠肺部攻击模型系统中均减弱。这些数据表明,唾液酸化的LOS糖型通过NTHi促进生物膜形成并在体内持续存在。

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