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Synthetic Pseudaminic-Acid-Based Antibacterial Vaccine Confers Effective Protection against Acinetobacter baumannii Infection
ACS Central Science ( IF 12.7 ) Pub Date : 2021-09-08 , DOI: 10.1021/acscentsci.1c00656
Ruohan Wei 1 , Xuemei Yang 2 , Han Liu 1 , Tongyao Wei 1 , Sheng Chen 2 , Xuechen Li 1
Affiliation  

Acinetobacter baumannii exhibits resistance to most first-line antibiotics; thus, development of new antibacterial agents is urgently required. Pseudaminic acid exists as the surface glycan of A. baumannii. In this study, we chemically synthesized pseudaminic acid, conjugated it to carrier protein CRM197 using the OPA (ortho-phthalaldehyde) chemistry, and obtained three Pse–CRM197 conjugates with different Pse loadings. These Pse–CRM197 conjugates were found to stimulate high immune responses in mice, which protected the vaccinated mice from infections caused by Pse-producing A. baumannii. Our data indicate that chemically synthesized Pse–CRM197 conjugates can be developed into vaccines against Pse-bearing pathogens, thus offering a feasible alternative for the control of clinical infections caused by multidrug-resistant (MDR) A. baumannii, for which current treatment options are extremely limited.

中文翻译:

合成假胺酸抗菌疫苗可有效预防鲍曼不动杆菌感染

鲍曼不动杆菌对大多数一线抗生素表现出耐药性;因此,迫切需要开发新的抗菌剂。假胺酸作为鲍曼不动杆菌的表面聚糖存在。在本研究中,我们化学合成了假胺酸,使用 OPA(苯二甲醛)化学将其与载体蛋白 CRM197 结合,并获得了三种具有不同 Pse 负载量的 Pse-CRM197 结合物。发现这些 Pse-CRM197 偶联物可刺激小鼠的高免疫反应,从而保护接种疫苗的小鼠免受由产 Pse鲍曼不动杆菌引起的感染. 我们的数据表明,化学合成的 Pse-CRM197 偶联物可以开发成针对携带 Pse 病原体的疫苗,从而为控制由多重耐药(MDR)鲍曼不动杆菌引起的临床感染提供可行的替代方案,目前的治疗方案是极其有限。
更新日期:2021-09-22
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