摘要
      sciuri葡萄球菌（目前也是哺乳动物sciuri球菌）是一种厌氧兼性和非运动性细菌，可导致心内膜炎、伤口感染、腹膜炎、尿路感染和感染性休克等重要的人类发病机制。一些耐甲氧西林金黄色葡萄球菌（MRSS）也会感染包括健康肉鸡、牛、狗和猪在内的动物。因此，耐甲氧西林金黄色葡萄球菌菌株的出现对健康构成了严重威胁，并促使科学界寻求新的治疗方案。在此，我们通过使用消减基因组学研究了S.sciuri的可药用基因组，该基因组学产生了7个基因/蛋白质，其中只有3个被预测为最终靶标。进一步挖掘文献表明，ArgS（WP_058610923）、SecY（WP_058811897）和MurA（WP_0585612677）参与了多药耐药性现象。建立并验证了3D蛋白同源性模型，然后对传统中药文库进行筛选（n = 36043种化合物）。分子对接和模拟研究通过确定其可药用潜力和最大氢键相互作用，揭示了对接的中药抑制剂在每个蛋白质靶标的可药用腔中的物理化学稳定性参数。RMSD图显示了由于螺旋-螺旋的结构变化和特定点的β-转β变化引起的波动。此外，由于“关系动力学”导致的蛋白质靶标的过渡变化显著影响受体-配体结合机制。据推测，这些发现可能有助于研究人员有力地发现和开发针对S.sciuri和其他肠道感染的有效疗法。
Abstract
Staphylococcus sciuri (also currently Mammaliicoccus sciuri) are anaerobic facultative and non-motile bacteria that causes significant human pathogenesis such as endocarditis, wound infections, peritonitis, UTI and septic shock. Some methicillin-resistant S. sciuri (MRSS) also infects animals that include healthy broilers, cattle, dogs and pigs. The emergence of MRSS strains thereby poses a serious health threat and thrives the scientific community towards novel treatment options. Herein, we investigated the druggable genome of S. sciuri by employing subtractive genomics that resulted in 7 genes/proteins where only 3 of them were predicted as final targets. Further mining the literature showed that the ArgS (WP_058610923), SecY (WP_058611897) and MurA (WP_058612677) are involved in multi-drug resistance phenomenon. The 3D protein homology models were built and validated, followed by screening against a Traditional Chinese Medicine library (n = 36,043 compounds). The molecular docking and simulation studies revealed the physicochemical stability parameters of the docked TCM inhibitors in the druggable cavities of each protein targets by identifying their druggability potential and maximum Hydrogen bonding interactions. The RMSD graph showed fluctuations due to structural changes in the helix-coil-helix and beta-turn-beta changes at specific points. Additionally, the transitional changes in protein targets due to “relational dynamics” significantly impact the receptor-ligand binding mechanism. It is assumed that such findings might facilitate researchers to robustly discover and develop effective therapeutics against S. sciuri alongside other enteric infections.

https://www.researchsquare.com/article/rs-2713405/v1