Department of Biochemistry, Central University of Rajasthan, Ajmer, Rajasthan, India.
Infect Immun. 2023 May 16;91(5):e0002323. doi: 10.1128/iai.00023-23. Epub 2023 Apr 5.
Acinetobacter baumannii causes hospital-acquired infections and is responsible for high mortality and morbidity. The interaction of this bacterium with the host is critical in bacterial pathogenesis and infection. Here, we report the interaction of peptidoglycan-associated lipoprotein (PAL) of A. baumannii with host fibronectin (FN) to find its therapeutic potential. The proteome of A. baumannii was explored in the host-pathogen interaction database to filter out the PAL of the bacterial outer membrane that interacts with the host's FN protein. This interaction was confirmed experimentally using purified recombinant PAL and pure FN protein. To investigate the pleiotropic role of PAL protein, different biochemical assays using wild-type PAL and PAL mutants were performed. The result showed that PAL mediates bacterial pathogenesis, adherence, and invasion in host pulmonary epithelial cells and has a role in the biofilm formation, bacterial motility, and membrane integrity of bacteria. All of the results suggest that PAL's interaction with FN plays a vital role in host-cell interaction. In addition, the PAL protein also interacts with Toll-like receptor 2 and MARCO receptor, which suggests the role of PAL protein in innate immune responses. We have also investigated the therapeutic potential of this protein for vaccine and therapeutic design. Using reverse vaccinology, PAL's potential epitopes were filtered out that exhibit binding potential with host major histocompatibility complex class I (MHC-I), MHC-II, and B cells, suggesting that PAL protein is a potential vaccine target. The immune simulation showed that PAL protein could elevate innate and adaptive immune response with the generation of memory cells and would have subsequent potential to eliminate bacterial infection. Therefore, the present study highlights the interaction ability of a novel host-pathogen interacting partner (PAL-FN) and uncovers its therapeutic potential to combat infection caused by A. baumannii.
鲍曼不动杆菌会引起医院获得性感染，是导致高死亡率和高发病率的主要原因。这种细菌与宿主的相互作用对细菌发病机制和感染至关重要。在这里，我们报告了鲍曼不动杆菌的肽聚糖相关脂蛋白（PAL）与宿主纤维连接蛋白（FN）的相互作用，以发现其治疗潜力。在宿主-病原体相互作用数据库中探索了鲍曼不动杆菌的蛋白质组，以筛选出与宿主 FN 蛋白相互作用的细菌外膜的 PAL。使用纯化的重组 PAL 和纯 FN 蛋白进行了实验来验证这种相互作用。为了研究 PAL 蛋白的多效性作用，使用野生型 PAL 和 PAL 突变体进行了不同的生化分析。结果表明，PAL 介导了细菌在宿主肺上皮细胞中的发病机制、黏附和侵袭，并在细菌生物膜形成、细菌运动性和膜完整性方面发挥作用。所有结果表明，PAL 与 FN 的相互作用在宿主细胞相互作用中起着至关重要的作用。此外，PAL 蛋白还与 Toll 样受体 2 和 MARCO 受体相互作用，这表明 PAL 蛋白在先天免疫反应中发挥作用。我们还研究了该蛋白在疫苗和治疗设计中的治疗潜力。使用反向疫苗学，筛选出了与宿主主要组织相容性复合体 I（MHC-I）、MHC-II 和 B 细胞具有结合潜力的 PAL 的潜在表位，表明 PAL 蛋白是一种潜在的疫苗靶标。免疫模拟表明，PAL 蛋白可以通过产生记忆细胞来提高先天和适应性免疫反应，并有可能随后消除细菌感染。因此，本研究强调了一种新的宿主-病原体相互作用伙伴（PAL-FN）的相互作用能力，并揭示了其治疗潜力，以对抗由鲍曼不动杆菌引起的感染。
