摘要

作为最具影响力和麻烦的人类致病菌之一，鲍曼不动杆菌已出现多种多药耐药菌株。收集33个完整的鲍曼不动杆菌基因组和84个有代表性的抗生素耐药决定簇后，我们使用Vaxign反向疫苗学方法来预测针对鲍曼不动杆菌感染的经典型候选疫苗和针对抗生素抗性的新型候选疫苗。我们的基因组分析鉴定出35个外膜或细胞外粘附素，其在所有33种基因组中保守，没有人蛋白质同源性，并且具有少于2个跨膜螺旋。这35种抗原包括11种TonB依赖性受体，8种孔蛋白，7种外排泵蛋白和2种菌毛蛋白（FilF和CAM87009.1）。预测CAM86003.1是3种抗生素敏感菌株缺失的粘附素外膜蛋白，并且在21种抗生素抗性菌株中保守。可行的抗病毒疫苗候选物还包括一种细胞外蛋白（QnrA），3种RND型外膜外排泵蛋白和3种CTX-M型β-内酰胺酶。在39种β-内酰胺酶中，鲍曼不动杆菌CTX-M-2，-5和-43酶被预测为粘附素和比其他β-内酰胺酶更好的候选疫苗以诱导预防性免疫和增强抗生素治疗。这份报告代表了第一个系统地预测针对微生物病原体的抗生素抗性的疫苗抗原候选物的反向疫苗学研究。

As one of the most influential and troublesome human pathogens, Acinetobacter baumannii (A. baumannii) has emerged with many multidrug-resistant strains. After collecting 33 complete A. baumannii genomes and 84 representative antibiotic resistance determinants, we used the Vaxign reverse vaccinology approach to predict classical type vaccine candidates against A. baumannii infections and new type vaccine candidates against antibiotic resistance. Our genome analysis identified 35 outer membrane or extracellular adhesins that are conserved among all 33 genomes, have no human protein homology, and have less than 2 transmembrane helices. These 35 antigens include 11 TonB dependent receptors, 8 porins, 7 efflux pump proteins, and 2 fimbrial proteins (FilF and CAM87009.1). CAM86003.1 was predicted to be an adhesin outer membrane protein absent from 3 antibiotic-sensitive strains and conserved in 21 antibiotic-resistant strains. Feasible anti-resistance vaccine candidates also include one extracellular protein (QnrA), 3 RND type outer membrane efflux pump proteins, and 3 CTX-M type β-lactamases. Among 39 β-lactamases, A. baumanniiCTX-M-2, -5, and -43 enzymes are predicted as adhesins and better vaccine candidates than other β-lactamases to induce preventive immunity and enhance antibiotic treatments. This report represents the first reverse vaccinology study to systematically predict vaccine antigen candidates against antibiotic resistance for a microbial pathogen. 

http://www.mdpi.com/1422-0067/18/2/458