Barh Debmalya, Kumar Anil
Institute of Integrative Omics and Applied Biotechnology (IIOAB), Nonakuri, India.
In Silico Biol. 2009;9(4):225-31.
Neisseria gonorrhoeae is responsible for causing gonorrhea, one of the most common sexually transmitted diseases prevailing globally. Although extensive researches are in progress in order to control the transmission of the disease and to develop drug(s) against the pathogen, till date no effective vaccine or specific drug could be developed and only antibiotic treatment is in use. Perhaps, due to excess use of antibiotics, several resistant strains have been found. In the present study, metabolic pathways-related candidate drug and vaccine targets have been identified in N. gonorrhoeae virulent strain FA 1090 using an in silico subtractive genomics approach. 106 putative drug targets out of 537 essential genes have been predicted. 67 cytoplasmic and 9 membrane enzymes, along with 10 membrane transporters are found to be the potential drug targets from the host-pathogen common metabolic pathways. Among these targets, competence lipoproteins (NGO0277) and cysW have been identified as candidate vaccine targets. 20 drug targets have been identified from pathogen specific unique metabolic pathways. Out of these, 6 enzymes are involved in dual metabolic pathways and 2 are expressed in cell wall and fimbrium. These gonococci-specific proteins are expected to be better possible drug targets. Screening of the functional inhibitors against these novel targets may result in discovery of novel therapeutic compounds that can be effective against antibiotic resistant strains.
淋病奈瑟菌是导致淋病的病原体,淋病是全球最常见的性传播疾病之一。尽管为了控制该疾病的传播以及研发针对该病原体的药物正在进行广泛研究,但迄今为止尚未开发出有效的疫苗或特效药物,目前仅使用抗生素治疗。或许由于抗生素的过度使用,已发现了几种耐药菌株。在本研究中,利用计算机减法基因组学方法在淋病奈瑟菌致病菌株FA 1090中鉴定出了与代谢途径相关的候选药物和疫苗靶点。在537个必需基因中预测出了106个假定的药物靶点。从宿主 - 病原体共同代谢途径中发现67种胞质酶和9种膜酶以及10种膜转运蛋白是潜在的药物靶点。在这些靶点中,感受态脂蛋白(NGO0277)和cysW已被鉴定为候选疫苗靶点。从病原体特异性独特代谢途径中鉴定出了20个药物靶点。其中,6种酶参与双重代谢途径,2种在细胞壁和菌毛中表达。这些淋病奈瑟菌特异性蛋白有望成为更好的潜在药物靶点。针对这些新靶点筛选功能性抑制剂可能会发现对耐药菌株有效的新型治疗化合物。