肺炎克雷伯菌
微生物学
补体系统
补体膜攻击复合物
替代补体途径
生物
经典补体途径
败血症
细菌
病菌
克雷伯菌
凝集素途径
大肠杆菌
抗体
免疫学
基因
生物化学
遗传学
作者
Katharina V. Opstrup,Tue Bjerg Bennike,Gunna Christiansen,Svend Birkelund
标识
DOI:10.1016/j.micinf.2022.105074
摘要
Klebsiella pneumoniae is an opportunistic gram-negative pathogen causing serious infections, including sepsis. In plasma, activation of the complement cascades is important for killing bacteria. Thirty clinical Klebsiella spp. blood isolates were analyzed for serum susceptibility in 75% normal human serum (NHS). Twenty-two were serum resistant and eight were serum sensitive, and subsequently tested in 5-75% NHS. Two isolates were killed in 5% and the remaining six in 50%-75% NHS. The two 5% sensitive isolates showed binding of complement (C)4 and C3 in 5% NHS with formation of membrane attack complex (MAC). Inhibition of the classical/lectin mediated pathways (CP/LP) using a C4 specific nanobody, hC4Nb8, led to survival of both isolates in 5% NHS. Using nanobody hC3Nb1, inhibiting the alternative pathway (AP), the isolates were killed in 5% NHS, and amplification of the CP/LP by AP was not necessary for killing. Sole AP killing of these isolates when inhibiting CP/LP with hC4Nb8 was observed in 50% NHS, stressing the concentration dependent functionality of AP. For the less sensitive isolates, killing required activation of CP/LP and AP demonstrated by inhibition with nanobodies. AP inhibition resulted in no C3 deposition on the serum resistant isolate, supporting that AP was the sole activation pathway.
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