Department of Health Science and Technology, Aalborg University, Fredrik Bajers Vej 3b, 9220, Aalborg, Denmark.
Department of Biomedicine, Aarhus University, Wilhelms Meyers Alle 4, 8000, Aarhus, Denmark.
Microbes Infect. 2020 Jan-Feb;22(1):19-30. doi: 10.1016/j.micinf.2019.08.003. Epub 2019 Aug 29.
The Gram-negative bacterium Klebsiella pneumoniae is an opportunistic pathogen, which can cause life-threatening infections such as sepsis. Worldwide, emerging multidrug resistant K. pneumoniae infections are challenging to treat, hence leading to increased mortality. Therefore, understanding the interactions between K. pneumoniae and the immune system is important to develop new treatment options. We characterized ten clinical K. pneumoniae isolates obtained from blood of bacteremia patients. The interaction of the isolates with human serum was investigated to elucidate how K. pneumoniae escapes the host immune system, and how complement activation by K. pneumoniae changed the capsule structure. All K. pneumoniae isolates activated the alternative complement pathway despite serum resistance of seven isolates. One serum sensitive isolate activated two or all three pathways, and this isolate was lysed and had numerous membrane attack complexes in the outer membrane. However, we also found deposition of complement components in the capsule of serum resistant isolates resulting in morphological capsule changes and capsule shedding. These bacteria did not lyse, and no membrane attack complex was observed despite deposition of C5b-9 within the capsule, indicating that the capsule of serum resistant K. pneumoniae isolates is a defense mechanism against complement-mediated lysis.
革兰氏阴性菌肺炎克雷伯菌是一种机会致病菌，可引起危及生命的感染，如败血症。在全球范围内，新出现的多药耐药肺炎克雷伯菌感染难以治疗，因此导致死亡率增加。因此，了解肺炎克雷伯菌与免疫系统之间的相互作用对于开发新的治疗方法很重要。我们对从菌血症患者血液中获得的 10 株临床肺炎克雷伯菌分离株进行了表征。研究了分离株与人血清的相互作用，以阐明肺炎克雷伯菌如何逃避宿主免疫系统，以及肺炎克雷伯菌激活补体如何改变荚膜结构。尽管有 7 株分离株对血清有抗性，但所有肺炎克雷伯菌分离株都激活了替代补体途径。一个血清敏感的分离株激活了两个或所有三个途径，并且这个分离株被裂解并且在外膜中有许多膜攻击复合物。然而，我们还发现补体成分在血清抗性分离株的荚膜中沉积，导致形态荚膜改变和荚膜脱落。这些细菌没有裂解，并且尽管在荚膜内沉积了 C5b-9，但没有观察到膜攻击复合物，表明血清抗性肺炎克雷伯菌分离株的荚膜是对补体介导的裂解的防御机制。
