Detection and characterization of bacterial polysaccharides in drug-resistant enterococci

Detection and characterization of bacterial polysaccharides in drug-resistant enterococci
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DOI:
10.1007/s10719-019-09881-3
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发表时间:
2019-10-01
影响因子:
3
通讯作者:
Sakinc, Turkan
Sakinc, Turkan
中科院分区:
生物学4区
文献类型:
--
作者:
Ali, Liaqat;Blum, Hubert E.;Sakinc, Turkan

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粪肠球菌(E. faecium)已成为当今卫生保健相关感染的主要原因之一,难以用现有抗生素治疗。这些病原体在细胞表面产生荚膜多糖,在粘附、毒力和逃逸中起重要作用。因此,我们的目标是鉴定和表征细菌多糖抗原,这是开发基于疫苗的预防方法的核心。采用脂磷胆酸(LTA)和二杂聚糖(DHG)一抗对粪肠杆菌及其突变株和补充株的粗细胞壁相关多糖进行了纯化和分析。耐药粪肠杆菌菌株可能具有新的荚膜多糖,使它们能够避免opsonic杀死的逃避。粪肠杆菌U0317菌株被一种针对整个细菌细胞的抗体anti-U0317(相似度95%)很好地调理。缺失突变体对青霉素结合蛋白(抗pbp -5)的调理噬细胞杀伤的易感性显著增加(90-95%)。相比之下,在小鼠尿路和大鼠心内膜炎感染模型中,毒力没有显著差异。本研究探讨了粪肠杆菌荚膜的生物学作用。研究结果表明,U0317菌株不仅对抗lta敏感,而且对其他肠球菌表面蛋白的抗体也敏感。我们的研究结果表明,多糖胶囊介导了对调理吞噬的抗性。我们还发现,在尿路细菌毒力和感染性心内膜炎的体内模型中,荚膜多糖没有发挥重要作用。
Enterococcus faecium (E. faecium) has emerged as one of today's leading causes of health care-associated infections that is difficult to treat with the available antibiotics. These pathogens produce capsular polysaccharides on the cell surface which play a significant role in adhesion, virulence and evasion. Therefore, we aimed at the identification and characterization of bacterial polysaccharide antigens which are central for the development of vaccine-based prophylactic approaches. The crude cell wall-associated polysaccharides from E. faecium, its mutant and complemented strains were purified and analyzed by a primary antibody raised against lipoteichoic acid (LTA) and diheteroglycan (DHG). The resistant E. faecium strains presumably possess novel capsular polysaccharides that allow them to avoid the evasion from opsonic killing. The E. faecium U0317 strain was very well opsonized by anti-U0317 (similar to 95%), an antibody against the whole bacterial cell. The deletion mutant showed a significantly increased susceptibility to opsonophagocytic killing (90-95%) against the penicillin binding protein (anti-PBP-5). By comparison, in a mouse urinary tract and rat endocarditis infection model, respectively, there were no significant differences in virulence. In this study we explored the biological role of the capsule of E. faecium. Our findings showed that the U0317 strain is not only sensitive to anti-LTA but also to antibodies against other enterococcal surface proteins. Our findings demonstrate that polysaccharides capsule mediated-resistance to opsonophagocytosis. We also found that the capsular polysaccharides do not play an important role in bacterial virulence in urinary tract and infective endocarditis in vivo models.