wu 20182 s

Pseudaminic acid on exopolysaccharide of Acinetobacter baumannii plays a critical role in phage-assisted preparation of glycoconjugate vaccine with high antigenicity

Infection by antibiotic resistant bacterial pathogens poses a serious global health threat. Therefore, a new therapy is urgently required to overcome the failure of antibiotic. Glycoconjugate vaccine have been proven to be effective in combating a broad spectrum of diseases caused by antibiotic resistant bacteria, and was suggested as a promising solution. In this regard, rising the efficacy of glycoonjugate preparation and biological activity of glycoconjugate-induced antibody will accelerate the development of vaccination. The research team lead by Dr. Shih-Hsiung Wu, a Distinguished Research Fellow in the institute of Biological Chemistry, and Dr. Chung-Yi Wu, a Research Fellow in the Genomic Research Center found that pseudaminic acid (Pse) plays a critical role on this field and these results had published in Journal of the American Chemical Society on July 2nd, 2018.

Pse has been known for participating in crucial bacterial virulence, such as Acinetobacter baumannii, and thus is an attractive target in the development of glycoconjugate vaccine. Also, Pse was found to be involved in the exopolysaccharide (EPS) of mild antibiotic resistant A. baumannii strain 54149 (Ab-54149) EPS of which specific glycosyl linkage can be depolymerized by phage ΦAB6 tailspike protein (ΦAB6TSP). In this study, we found that the antibodies induced by Ab-54149 EPS was capable ofrecognizing a range of EPS of other clinical A. baumannii strains, and deemed as a great potential material for vaccination. To efficiently acquire homogeneous EPS-derived oligosaccharide with significant immunogenic activity for the production of glycoconjugate, we used the ΦAB6TSP for the fragmentation of Ab-54149 EPS instead of chemical methods. Moreover, insight into the ligand binding characterization of ΦAB6TSP suggested the branched Pse on the Ab-54149 EPS served as a recognition site of ΦAB6TSP. The serum boosted by ΦAB6TSP-digested product and carrier protein CRM197 conjugate complex displayed specific sensitivity toward Ab-54149 EPS with bacterial killing activity. Strikingly, Pse is an ideal epitope with strong antigenicity, profiting the application of the probe for pathogen detection and glyco-based vaccine.

The Full research article : https://pubs.acs.org/doi/10.1021/jacs.8b04078

Authors: I-Ming Lee, Feng-Ling Yang, Te-Li, Chen, Kuo-Shiang Liao, Chien-Tai Ren, Nien-Tsung Lin, Yu-Pei Chang, Chung-Yi Wu* and Shih-Hsiung Wu*

Updated : 2018.07.30

wu 2018 pse toc