iHUB Drishti Foundation, Indian Institute of Technology, Jodhpur, Rajasthan 342030, India.
Smart Healthcare Department, Interdisciplinary Research Platform, Indian Institute of Technology, Jodhpur, Rajasthan 342030, India.
ACS Appl Bio Mater. 2024 Jun 17;7(6):4142-4161. doi: 10.1021/acsabm.4c00466. Epub 2024 May 21.
The emergence of antimicrobial resistance, exemplified by methicillin-resistant (MRSA), poses a grave threat to public health globally. Over time, MRSA has evolved resistance to multiple antibiotics, challenging conventional treatment strategies. The relentless adaptability of MRSA underscores the urgent need for innovative and targeted antimicrobial approaches to combat this resilient pathogen. Ancient knowledge and practices, along with scientific evidence, have established that metallic copper, and its organic coordination complexes can act as potential antibacterial substances. In search of a smart and effective antimicrobial against MRSA, we designed, synthesized, and characterized a bidentate copper(II) ligand complex (SG-Cu) utilizing a comprehensive array of analytical techniques, including ESI-MS, elemental analysis, X-ray photoelectron spectroscopy, electron paramagnetic resonance spectroscopy, and others. Antibacterial efficacy and mechanism of action of the complex were assessed through bacterial growth analyses, bacterial membrane perturbation assays, ROS elicitation assays, and field emission scanning electron microscopy. SG-Cu was found to maintain robust biocompatibility against the mammalian cell lines HEK-293, WI-38, and NIH/3T3. Remarkably, SG-Cu demonstrated significant biofilm disruptive tendency evidenced by the retardation of sliding motility, reduction in slime production, reduction in biofilm viability, and enhanced biofilm eradication, both and in urinary catheters. studies on murine excisional wounds, with SG-Cu impregnated in a palmitic acid conjugated NAVSIQ hexapeptide (PA-NV) hydrogel, revealed the sustained release of SG-Cu from the gel matrix, facilitating accelerated wound healing and effective wound disinfection. This multifaceted investigation highlights the potential of SG-Cu as a versatile option for combating MRSA infections and promoting wound healing, solidifying its claim to be developed into a viable therapeutic.
耐甲氧西林金黄色葡萄球菌（MRSA）的出现代表了一种严重的全球公共卫生威胁。随着时间的推移，MRSA 已经对多种抗生素产生了耐药性，这对传统的治疗策略构成了挑战。MRSA 的无情适应性突显了迫切需要创新和靶向的抗菌方法来对抗这种具有弹性的病原体。古老的知识和实践，以及科学证据，已经证明金属铜及其有机配位化合物可以作为潜在的抗菌物质。为了寻找一种针对 MRSA 的智能且有效的抗菌剂，我们设计、合成并通过一系列分析技术（包括 ESI-MS、元素分析、X 射线光电子能谱、电子顺磁共振谱等）对二价铜配合物（SG-Cu）进行了表征。通过细菌生长分析、细菌膜扰动实验、ROS 诱导实验和场发射扫描电子显微镜观察评估了该配合物的抗菌效果和作用机制。研究发现，SG-Cu 对哺乳动物细胞系 HEK-293、WI-38 和 NIH/3T3 均具有较强的生物相容性。令人瞩目的是，SG-Cu 表现出显著的生物膜破坏倾向，可减缓滑动运动、减少黏液产生、降低生物膜活性和增强生物膜清除，这些作用在尿路导管中也得到了验证。此外，在载有 SG-Cu 的棕榈酸偶联 NAVSIQ 六肽（PA-NV）水凝胶的鼠切创模型中进行的体内研究表明，SG-Cu 可以从水凝胶基质中持续释放，从而促进伤口愈合和有效消毒。这项多方面的研究突出了 SG-Cu 作为一种对抗 MRSA 感染和促进伤口愈合的多功能选择的潜力，为其进一步开发为可行的治疗方法提供了坚实的依据。
