A vaccine candidate for the treatment of extensively drug-resistant (XDR) Acinetobacter baumannii

• Main Authors: Wen-Jie Shen, 沈文傑
• Other Authors: 吳世雄
• Format: Others
• Language: en_US
• Published: 2017
• Online Access: http://ndltd.ncl.edu.tw/handle/32887645303285336831

碩士 === 國立臺灣大學 === 生化科學研究所 === 105 === Multidrug resistance in bacteria is always a global health problem. According to the Taiwan Nosocomial Infections Surveillance System, the ratio of carbapenem-resistant Acinetobacter baumannii increased from 3.4% in 2002 to 72.6% in 2016. Since carbapenems are the last line of antibiotics used for the treatment of gram-negative bacteria, developing new therapeutic strategies against multidrug-resistant A. baumannii is urgent. Capsular polysaccharide (CPS) is a virulence factor of A. baumannii. In our previous study, the CPS-induced antibody provided 55% protection in the animal model. A. baumannii was reported to have a bifurcated pathway for both O-glycosylation in some outer membrane proteins and capsule biosynthesis. Therefore, CPS-anchored outer membrane proteins might serve as natural glycoconjugate vaccines to effectively activate adaptive immunity. In this study, we identified Omp38 as a virulence-relevant vaccine candidate along with its CPS-anchoring position. Together with the CPS-specific antibody and mass-based strategy, the antibody-enriched glycoproteins were subjected to perform a mild -elimination followed by Michael addition of dithiothreitol (BEMAD). These thereby led to the discovery of six highly potential glycosylation sites, 306S, 307T, 90S, 166S, 338S, 334T, on Omp38. As a summary, this study has provided a better insight into the development of the new class of vaccine candidate against extensively drug-resistant (XDR) A. baumannii.