Abstract:
Overuse of antimicrobials has greatly contributed to the increase in the emergence of multidrug-resistant bacteria, a situation that hinders the control and treatment of infectious diseases. This is the case with urinary tract infections (UTIs), which represent a substantial percentage of worldwide public health problems, thus the need to look for alternatives for their control and treatment. Previous studies have shown the usefulness of autologous bacterial lysates as an alternative for the treatment and control of UTIs. However, a limitation is the high cost of producing individual immunogens. At the same time, an important aspect of vaccines is their immunogenic amplitude, which is the reason why they must be constituted of diverse antigenic components. In the case of UTIs, the etiology of the disease is associated with different bacteria, and even Escherichia coli, the main causal agent of the disease, is made up of several antigenic variants. In this work, we present results on the study of a bacterial lysate composed of 10 serotypes of Escherichia coli and by Klebsiella pneumoniae, Klebsiella aerogenes, Enterococcus faecalis, Proteus mirabilis, Citrobacter freundii, and Staphylococcus haemolyticus. The safety of the compound was tested on cells in culture and in an animal model, and its immunogenic capacity by analysing in vitro human and murine macrophages (cell line J774 A1). The results show that the polyvalent lysate did not cause damage to the cells in culture or alterations in the animal model used. The immunostimulatory activity assay showed that it activates the secretion of TNF-α and IL-6 in human macrophages and TNF-α in murine cells. The obtained results suggest that the polyvalent lysate evaluated can be an alternative for the treatment and control of chronic urinary tract infections, which will reduce the use of antimicrobials.
摘要:
抗生素的过度使用极大地促进了多药耐药菌的出现增加,一种阻碍传染病控制和治疗的情况。尿路感染(UTI)就是这种情况,占全球公共卫生问题的很大一部分,因此,需要寻找替代方案来控制和治疗它们。先前的研究表明,自体细菌裂解物作为治疗和控制UTI的替代方法是有用的。然而,限制是生产单个免疫原的高成本。同时,疫苗的一个重要方面是它们的免疫原性幅度,这就是为什么它们必须由不同的抗原成分组成的原因。在UTI的情况下,该疾病的病因与不同的细菌有关,甚至大肠杆菌,疾病的主要病因,由几种抗原变体组成。在这项工作中,我们介绍了由10种血清型大肠杆菌和肺炎克雷伯菌组成的细菌裂解物的研究结果,产气克雷伯菌,粪肠球菌,变形杆菌,Freundii柠檬酸杆菌,和溶血葡萄球菌.在培养的细胞和动物模型中测试了该化合物的安全性,通过分析体外人和鼠巨噬细胞(细胞系J774A1)和其免疫原性能力。结果表明,多价裂解物不引起对培养物中细胞的损伤或在所用动物模型中的改变。免疫刺激活性分析表明,它激活了人巨噬细胞中TNF-α和IL-6的分泌,并激活了小鼠细胞中TNF-α的分泌。获得的结果表明,评估的多价裂解物可以替代治疗和控制慢性尿路感染,这将减少抗菌药物的使用。