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Identification of membrane associated drug targets in Borrelia burgdorferi ZS7- subtractive genomics approach

机译:鉴定伯氏疏螺旋体ZS7-消减基因组学方法中的膜相关药物靶标

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摘要

Lyme disease is an infectious disease caused by a spirochete Borrelia burgdorferi ZS7. This spirochete is most often spread by ticks. Single antibiotic therapy is sufficient for containment of the early stage progression of the disease but combinational therapy is more preferred in later stages. Research is in progress for the development of drugs against the pathogen, but till date no vaccines have been developed to effect the late stage infections. There is a rapid rise in the cases of antibiotic-resistant population which is more than 10% of the total infected individuals. In such condition vaccine becomes the sole alternative for prevention. Therefore effective treatment includes antibiotic combination and combination of antigenic surfaces (for vaccine preparation). Thus, a comprehensive list of drug targets unique to the microorganisms is often necessary. Availability of Borrelia burgdorferi ZS7 proteome has enabled insilico analysis of protein sequences for the identification of drug targets and vaccine targets. In this study, 272 essential proteins were identified out of which 42 proteins were unique to the microorganism. The study identified 15 membrane localized drug targets. Amongst these 15, molecular modeling and structure validation of the five membrane localized drug target proteins could only be achieved because of the low sequence identity of the remaining proteins with RCSB structures. These 3D structures can be further characterized by invitro and invivo studies for the development of novel vaccine epitopes and novel antibiotic therapy against Borrelia burgdorferi.
机译:莱姆病是由螺旋体伯氏疏螺旋体ZS7引起的传染病。这种螺旋体最常通过壁虱传播。单一抗生素治疗足以遏制疾病的早期进展,但在晚期则更优选联合治疗。研发抗病原体药物的研究正在进行中,但是迄今为止,尚未开发出能够影响晚期感染的疫苗。抗生素耐药性病例迅速增加,占总感染人数的10%以上。在这种情况下,疫苗成为预防的唯一选择。因此,有效的治疗包括抗生素组合和抗原表面组合(用于疫苗制备)。因此,通常需要微生物独特的药物靶标的完整列表。伯氏疏螺旋体ZS7蛋白质组的可用性使得能够对蛋白质序列进行计算机分析,以鉴定药物靶标和疫苗靶标。在这项研究中,鉴定出272种必需蛋白质,其中42种蛋白质是微生物特有的。该研究确定了15个膜定位的药物靶标。在这15种中,仅能对五个膜定位的药物靶蛋白进行分子建模和结构验证,因为其余具有RCSB结构的蛋白的序列同一性较低。这些3D结构可以通过体内和体内研究进一步表征,以开发新型疫苗抗原决定簇和新型抗伯氏疏螺旋体的抗生素疗法。

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