Department of General and Environmental Microbiology, Institute of Biology and Sport Biology, University of Pécs, Ifusag utja. 6, 7624 Pecs, Hungary.
Department of Agricultural Biotechnology, Assam Agricultural University, Jorhat 785013, India.
Molecules. 2022 Mar 24;27(7):2083. doi: 10.3390/molecules27072083.
Methicillin-resistant (MRSA) is an opportunistic pathogen and responsible for causing life-threatening infections. The emergence of hypervirulent and multidrug-resistant (MDR) strains led to challenging issues in antibiotic therapy. Consequently, the morbidity and mortality rates caused by infections have a substantial impact on health concerns. The current worldwide prevalence of MRSA infections highlights the need for long-lasting preventive measures and strategies. Unfortunately, effective measures are limited. In this study, we focus on the identification of vaccine candidates and drug target proteins against the 16 strains of MRSA using reverse vaccinology and subtractive genomics approaches. Using the reverse vaccinology approach, 4 putative antigenic proteins were identified; among these, PrsA and EssA proteins were found to be more promising vaccine candidates. We applied a molecular docking approach of selected 8 drug target proteins with the drug-like molecules, revealing that the ZINC4235426 as potential drug molecule with favorable interactions with the target active site residues of 5 drug target proteins , biotin protein ligase, HPr kinase/phosphorylase, thymidylate kinase, UDP-N-acetylmuramoyl-L-alanyl-D-glutamate-L-lysine ligase, and pantothenate synthetase. Thus, the identified proteins can be used for further rational drug or vaccine design to identify novel therapeutic agents for the treatment of multidrug-resistant staphylococcal infection.
耐甲氧西林金黄色葡萄球菌（MRSA）是一种机会性病原体，可导致危及生命的感染。高毒力和多药耐药（MDR）菌株的出现给抗生素治疗带来了挑战。因此，感染引起的发病率和死亡率对健康问题有重大影响。目前全球范围内 MRSA 感染的流行情况表明，需要采取持久的预防措施和策略。不幸的是，有效的措施有限。在这项研究中，我们使用反向疫苗学和消减基因组学方法，针对 16 株 MRSA 鉴定疫苗候选物和药物靶蛋白。使用反向疫苗学方法，鉴定出 4 种假定的抗原蛋白；其中，PrsA 和 EssA 蛋白被认为是更有前途的疫苗候选物。我们应用分子对接方法，将 8 种候选药物靶蛋白与类药分子进行对接，结果表明，ZINC4235426 是一种有潜力的药物分子，与 5 种药物靶蛋白（生物素蛋白连接酶、HPr 激酶/磷酸化酶、胸苷酸激酶、UDP-N-乙酰胞壁酰-L-丙氨酰-D-谷氨酰-L-赖氨酰连接酶和泛酸合成酶）的靶活性位点残基具有良好的相互作用。因此，鉴定出的蛋白可用于进一步的合理药物或疫苗设计，以鉴定出治疗多药耐药性葡萄球菌感染的新型治疗剂。
