Rahman Anisur, Noore Sanaullah, Hasan Anayet, Ullah Rakib, Rahman Hafijur, Hossain Amzad, Ali Yeasmeen, Islam Saiful
Department of Genetic Engineering and Biotechnology, Faculty of Biological Sciences, University Of Chittagong, Chittagong-4331, Bangladesh.
Department of Genetic Engineering and Biotechnology, Faculty of Biological Sciences, University Of Chittagong, Chittagong-4331, Bangladesh.
Comput Biol Chem. 2014 Oct;52:66-72. doi: 10.1016/j.compbiolchem.2014.09.005. Epub 2014 Sep 18.
Bacillus anthracis is a gram positive, spore forming, rod shaped bacteria which is the etiologic agent of anthrax - cutaneous, pulmonary and gastrointestinal. A recent outbreak of anthrax in a tropical region uncovered natural and in vitro resistance against penicillin, ciprofloxacin, quinolone due to over exposure of the pathogen to these antibiotics. This fact combined with the ongoing threat of using B. anthracis as a biological weapon proves that the identification of new therapeutic targets is urgently needed.
In this computational approach various databases and online based servers were used to detect essential proteins of B. anthracis A0248. Protein sequences of B. anthracis A0248 strain were retrieved from the NCBI database which was then run in CD-hit suite for clustering. NCBI BlastP against the human proteome and similarity search against DEG were done to find out essential human non-homologous proteins. Proteins involved in unique pathways were analyzed using KEGG genome database and PSORTb, CELLO v.2.5, ngLOC - these three tools were used to deduce putative cell surface proteins.
Successive analysis revealed 116 proteins to be essential human non-homologs among which 17 were involved in unique metabolic pathways and 28 were predicted as membrane associated proteins. Both types of proteins can be exploited as they are unlikely to have homologous counterparts in the human host.
Being human non-homologous, these proteins can be targeted for potential therapeutic drug development in future. Targets on unique metabolic and membrane-bound proteins can block cell wall synthesis, bacterial replication and signal transduction respectively.
炭疽芽孢杆菌是一种革兰氏阳性、形成芽孢的杆状细菌，是炭疽病（皮肤炭疽、肺炭疽和胃肠炭疽）的病原体。最近在一个热带地区爆发的炭疽疫情发现，由于病原体过度接触这些抗生素，出现了对青霉素、环丙沙星、喹诺酮的天然及体外耐药性。这一事实加上将炭疽芽孢杆菌用作生物武器的持续威胁，证明迫切需要确定新的治疗靶点。
在这种计算方法中，使用了各种数据库和在线服务器来检测炭疽芽孢杆菌A0248的必需蛋白。从NCBI数据库检索炭疽芽孢杆菌A0248菌株的蛋白质序列，然后在CD-hit套件中运行以进行聚类。针对人类蛋白质组进行NCBI BlastP并针对DEG进行相似性搜索，以找出必需的人类非同源蛋白。使用KEGG基因组数据库以及PSORTb、CELLO v.2.5、ngLOC这三个工具对参与独特途径的蛋白质进行分析，以推断假定的细胞表面蛋白。
连续分析显示，有116种蛋白质是必需的人类非同源蛋白，其中17种参与独特的代谢途径，28种被预测为膜相关蛋白。这两种类型的蛋白质都可以被利用，因为它们在人类宿主中不太可能有同源对应物。
由于这些蛋白质是人类非同源的，未来可将其作为潜在治疗药物开发的靶点。针对独特代谢蛋白和膜结合蛋白的靶点可分别阻断细胞壁合成、细菌复制和信号转导。
