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The K1 Capsular Polysaccharide from Acinetobacter baumannii Is a Potential Therapeutic Target via Passive Immunization

机译:鲍曼不动杆菌的K1荚膜多糖是通过被动免疫的潜在治疗靶标

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The emergence of extremely resistant and panresistant Gram-negative bacilli, such as Acinetobacter baumannii, requires consideration of nonantimicrobial therapeutic approaches. The goal of this report was to evaluate the K1 capsular polysaccharide from A. baumannii as a passive immunization target. Its structure was determined by a combination of mass spectrometric and nuclear magnetic resonance (NMR) techniques. Molecular mimics that might raise the concern for autoimmune disease were not identified. Immunization of CD1 mice demonstrated that the K1 capsule is immunogenic. The monoclonal antibody (MAb) 13D6, which is directed against the K1 capsule from A. baumannii, was used to determine the seroprevalence of the K1 capsule in a collection of 100 A. baumannii strains. Thirteen percent of the A. baumannii isolates from this collection were seroreactive to MAb 13D6. Opsonization of K1-positive strains, but not K1-negative strains, with MAb 13D6 significantly increased neutrophil-mediated bactericidal activity in vitro (P P < 0.0001). These data support the proof of principle that the K1 capsule is a potential therapeutic target via passive immunization. Other serotypes require assessment, and pragmatic challenges exist, such as the need to serotype infecting strains and utilize serotype-specific therapy. Nonetheless, this approach may become an important therapeutic option with increasing antimicrobial resistance and a diminishing number of active antimicrobials.
机译:耐药性和泛耐药性的革兰氏阴性杆菌(如鲍曼不动杆菌)的出现,需要考虑使用非抗菌治疗方法。该报告的目的是评估鲍曼不动杆菌的K1荚膜多糖作为被动免疫靶标。它的结构是通过质谱和核磁共振(NMR)技术的结合来确定的。没有发现可能引起自身免疫性疾病的分子模拟物。 CD1小鼠的免疫证明K1胶囊具有免疫原性。针对来自鲍曼不动杆菌的K1胶囊的单克隆抗体(MAb)13D6用于确定100株鲍曼不动杆菌菌株中K1胶囊的血清阳性率。该集合中13%的鲍曼不动杆菌分离株对MAb 13D6具有血清反应活性。用MAb 13D6对K1阳性菌株进行调理,而不对K1阴性菌株进行调理,可显着提高体外中性粒细胞介导的杀菌活性(P P <0.0001)。这些数据支持原理证明K1胶囊是通过被动免疫的潜在治疗靶标。其他血清型需要评估,并且存在实际的挑战,例如需要对感染菌株进行血清分型并利用血清型特异性疗法。尽管如此,随着抗微生物药耐药性的增加和活性抗微生物药数量的减少,该方法可能成为重要的治疗选择。

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