Prado Ligia Carolina da Silva, Giacchetto Felice Andrei, Rodrigues Thaís Cristina Vilela, Tiwari Sandeep, Andrade Bruno Silva, Kato Rodrigo Bentes, Oliveira Carlo José Freire, Silva Marcos Vinicius, Barh Debmalya, Azevedo Vasco Ariston de Carvalho, Jaiswal Arun Kumar, Soares Siomar de Castro
Inter-unit Post-Graduate Program in Bioinformatics, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
Department of Microbiology, Immunology and Parasitology, Institute of Biological and Natural Sciences, Federal University of Triângulo Mineiro, Uberaba, MG, Brazil.
J Biomol Struct Dyn. 2022;40(20):10106-10121. doi: 10.1080/07391102.2021.1942211. Epub 2021 Jun 30.
The Gram-negative bacillus a member of family, is an opportunistic nosocomial pathogen commonly found in hospital outbreaks that can cause infections in the urinary tract, bloodstream, central nervous system and pneumonia. Because strains are resistant to several antibiotics, it is critical the need for effective treatments, including new drugs and vaccines. Here, we applied reverse vaccinology and subtractive genomic approaches for the prediction of potential vaccine and drug targets against 59 strains of . We found 759 core non-host homologous proteins, of which 87 are putative surface-exposed proteins, 183 secreted proteins, and 80 membrane proteins. From these proteins, we predicted seven candidates vaccine targets: a sn-glycerol-3-phosphate-binding periplasmic protein UgpB, a vitamin B12 TonB-dependent receptor, a ferrichrome porin FhuA, a divisome-associated lipoprotein YraP, a membrane-bound lytic murein transglycosylase A, a peptidoglycan lytic exotransglycosylase, and a DUF481 domain-containing protein. We also predicted two drug targets: a N(4)-acetylcytidine amidohydrolase, and a DUF1428 family protein. Using the molecular docking approach for each drug target, we identified and selected ZINC04259491 and ZINC04235390 molecules as the most favorable interactions with the target active site residues. Our findings may contribute to the development of vaccines and new drug targets against Communicated by Ramaswamy H. Sarma.
革兰氏阴性杆菌是该菌科的一员,是一种机会性医院病原体,常见于医院感染暴发中,可导致尿路感染、血流感染、中枢神经系统感染和肺炎。由于该菌株对多种抗生素耐药,因此开发包括新药和疫苗在内的有效治疗方法至关重要。在此,我们应用反向疫苗学和消减基因组方法来预测针对59株该菌的潜在疫苗和药物靶点。我们发现了759个核心非宿主同源蛋白,其中87个是推定的表面暴露蛋白,183个是分泌蛋白,80个是膜蛋白。从这些蛋白中,我们预测了七个候选疫苗靶点:一种sn-甘油-3-磷酸结合周质蛋白UgpB、一种维生素B12 TonB依赖性受体、一种高铁载体孔蛋白FhuA、一种与分裂体相关的脂蛋白YraP、一种膜结合溶菌胞壁质转糖基酶A、一种肽聚糖溶菌外转糖基酶和一种含DUF481结构域的蛋白。我们还预测了两个药物靶点:一种N(4)-乙酰胞苷酰胺水解酶和一种DUF1428家族蛋白。通过对每个药物靶点使用分子对接方法,我们鉴定并选择了ZINC04259491和ZINC04235390分子作为与靶点活性位点残基最有利的相互作用分子。我们的研究结果可能有助于开发针对该菌的疫苗和新的药物靶点。由拉马斯瓦米·H·萨尔马通讯。