Habibi Mehri, Asadi Karam Mohammad Reza, Bouzari Saeid
Department of Molecular Biology, Pasteur Institute of Iran, Pasteur Ave., Tehran 13164, Iran.
Department of Molecular Biology, Pasteur Institute of Iran, Pasteur Ave., Tehran 13164, Iran.
Microb Pathog. 2017 Sep;110:477-483. doi: 10.1016/j.micpath.2017.07.037. Epub 2017 Jul 25.
Uropathogenic Escherichia coli (UPEC) are among the most prevalent agents of urinary tract infections (UTIs). Antibiotic resistance reaches the need for alternative treatment approaches such as vaccination against UTIs. There is no ideal vaccine against UTIs, thus there is a need to evaluate different targets of uropathogens against UTIs. Ferric scavenger receptor FyuA in UPEC has the properties of an ideal vaccine candidate against UTIs. In the present study, the prevalence of FyuA among UPEC isolates, its immunogenicity with and without alum adjuvant, and its efficacy against experimental UTI were assessed. Totally, fyuA gene was present in 77% of the UPEC isolates tested. Alignments of FyuA exhibited a high degree of conservation among different submitted UPEC isolates in GenBank. The bioinformatics studies showed the high confidence value and stability of the FyuA structure. SDS-PAGE and Western blot confirmed the purification of FyuA with high yield by nickel resins. Mice vaccinated subcutaneously with the FyuA induced a significantly higher humoral response (total IgG, IgG1 and IgG2a) than control mice that alum enhanced these responses. The FuyA alone showed the ability to reduce the colonization of UPEC in bladder and kidney of mice as compared to the control group. But the addition of alum to FyuA increased the protection level against UPEC in these organs. Since, FyuA induced significant IgG1 (Th2) and IgG2a (Th1) responses and protected the mice against experimental UTI, it could be a promising target against UPEC infections.
尿路致病性大肠杆菌(UPEC)是尿路感染(UTIs)最常见的病原体之一。抗生素耐药性使得需要诸如针对尿路感染的疫苗接种等替代治疗方法。目前尚无理想的抗尿路感染疫苗,因此有必要评估尿路病原体针对尿路感染的不同靶点。UPEC中的铁清除受体FyuA具有成为抗尿路感染理想疫苗候选物的特性。在本研究中,评估了FyuA在UPEC分离株中的流行情况、其在有无明矾佐剂情况下的免疫原性以及其对实验性尿路感染的疗效。总共,在所测试的UPEC分离株中,77%存在fyuA基因。FyuA的比对显示在GenBank中不同提交的UPEC分离株之间具有高度保守性。生物信息学研究表明FyuA结构具有高置信度值和稳定性。SDS-PAGE和蛋白质印迹证实通过镍树脂可高产率纯化FyuA。皮下接种FyuA的小鼠诱导的体液反应(总IgG、IgG1和IgG2a)明显高于对照组小鼠,明矾可增强这些反应。与对照组相比,单独的FuyA显示出降低UPEC在小鼠膀胱和肾脏中定植的能力。但在FyuA中添加明矾可提高在这些器官中针对UPEC的保护水平。由于FyuA诱导了显著的IgG1(Th2)和IgG2a(Th1)反应并保护小鼠免受实验性尿路感染,它可能是对抗UPEC感染的一个有前景的靶点。