Section Pediatric Infectious Diseases, Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, the Netherlands.
Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands.
Infect Immun. 2019 May 21;87(6). doi: 10.1128/IAI.00077-19. Print 2019 Jun.
Although nontypeable (NTHi) is a human-specific nasopharyngeal commensal bacterium, it also causes upper respiratory tract infections in children and lower respiratory tract infections in the elderly, resulting in frequent antibiotic use. The transition from symbiotic colonizing bacterium to opportunistic pathogen is not completely understood. Incorporation of sialic acids into lipooligosaccharides is thought to play an important role in bacterial virulence. It has been known for more than 25 years that sialic acids increase resistance to complement-mediated killing; however, the mechanism of action has not been elucidated thus far. Here, we provide evidence that growth of NTHi in the presence of sialic acids Neu5Ac and Neu5Gc decreases complement-mediated killing through abrogating the classical pathway of complement activation by preventing mainly IgM antibody binding to the bacterial surface. Therefore, strategies that interfere with uptake or incorporation of sialic acids into the lipooligosaccharide, such as novel antibiotics and vaccines, might be worth exploring to prevent or treat NTHi infections.
虽然非定型 （NTHi） 是一种特定于人类的鼻咽共生菌，但它也会导致儿童上呼吸道感染和老年人下呼吸道感染，导致频繁使用抗生素。从共生定植菌到机会性病原体的转变尚不完全清楚。唾液酸的掺入到脂寡糖中被认为在细菌毒力中起重要作用。 超过 25 年以来，人们已经知道唾液酸增加了对补体介导杀伤的抵抗力; 然而，迄今为止，其作用机制尚未阐明。在这里，我们提供的证据表明，在存在唾液酸 Neu5Ac 和 Neu5Gc 的情况下生长的 NTHi 通过阻止主要的 IgM 抗体结合到细菌表面，从而通过消除补体激活的经典途径来减少补体介导的杀伤。因此，干扰唾液酸摄取或掺入脂寡糖的策略，例如新型抗生素和疫苗，可能值得探索以预防或治疗 NTHi 感染。
