评估使用合成和生物制品作为诊断靶向剂的潜力,成像,特别是抗生素抗性病原体引起的感染的治疗对于控制感染是重要的。我们检查了φ11溶源性噬菌体的受体结合蛋白Gp45之间的相互作用,和它的宿主金黄色葡萄球菌,医院感染的常见原因。利用分子动力学和对接模拟,我们鉴定了通过Gp45与金黄色葡萄球菌壁磷壁酸结合的肽。我们使用显微镜比较了Gp45和两个得分最高的肽序列(P1和P3)及其杂乱形式的结合亲和力,光谱学,和ELISA。我们的结果表明,与所有其他肽相比,rGp45(重组Gp45)和化学合成的P1对金黄色葡萄球菌具有更高的结合亲和力,除了大肠杆菌。此外,rGp45具有超过86%的捕获效率;P1具有超过64%的捕获效率。总的来说,我们的研究结果表明,受体结合蛋白,如rGp45,提供了一个关键的启动噬菌体生命周期的宿主吸附,可能在诊断中起重要作用,成像,针对细菌感染。因此,研究这些蛋白质可以开发控制感染的有效策略。
BACKGROUND: Evaluating the potential of using both synthetic and biological products as targeting agents for the diagnosis, imaging, and treatment of infections due to particularly antibiotic-resistant pathogens is important for controlling infections. This study examined the interaction between Gp45, a receptor-binding protein of the ϕ11 lysogenic phage, and its host Staphylococcus aureus (S. aureus), a common cause of nosocomial infections.
METHODS: Using molecular dynamics and docking simulations, this study identified the peptides that bind to S. aureus wall teichoic acids via Gp45. It compared the binding affinity of Gp45 and the two highest-scoring peptide sequences (P1 and P3) and their scrambled forms using microscopy, spectroscopy, and ELISA.
RESULTS: It was found that rGp45 (recombinant Gp45) and chemically synthesised P1 had a higher binding affinity for S. aureus compared with all other peptides, except for Escherichia coli. Furthermore, rGp45 had a capture efficiency of > 86%; P1 had a capture efficiency of > 64%.
CONCLUSIONS: These findings suggest that receptor-binding proteins such as rGp45, which provide a critical initiation of the phage life cycle for host adsorption, might play an important role in the diagnosis, imaging, and targeting of bacterial infections. Studying such proteins could accordingly enable the development of effective strategies for controlling infections.