Department of Microbiology, Soochow University, Taipei, Taiwan.
Research Center for Food and Cosmetic Safety and Research Center for Chinese Herbal Medicine, Chang Gung University of Science and Technology, Kweishan, Taoyuan, Taiwan; Department of Anesthesiology, Chang Gung Memorial Hospital, Taoyuan, Taiwan; Department of Cosmetic Science, Chang Gung University of Science and Technology, Kweishan, Taoyuan, Taiwan.
Biomed Pharmacother. 2023 Sep;165:115017. doi: 10.1016/j.biopha.2023.115017. Epub 2023 Jun 14.
The emergence of multidrug-resistant bacteria contributes to the necessity of developing novel infection treatment approaches. This study was designed to evaluate the antimicrobial and wound healing activities of platelet-rich plasma (PRP) in combination with β-lactams (ampicillin and/or oxacillin) for the application on methicillin-resistant Staphylococcus aureus (MRSA)-infected skin. PRP was collected from the peripheral blood of healthy donors. The anti-MRSA activity was tested through a growth inhibition curve, colony-forming unit (CFU), and SYTO 9 assay. The PRP incorporation lowered the minimum inhibitory concentration (MIC) of ampicillin and oxacillin against MRSA. The combination of β-lactams together with PRP showed a three-log CFU reduction of MRSA. The major components of PRP for eliminating MRSA were found to be the complement system and iron sequestration proteins, according to the proteomic analysis. The adhesive bacterial colony in the microplate was decreased from 2.9 × 10 to 7.3 × 10 CFU after the treatment of cocktails containing β-lactams and PRP. The cell-based study indicated that keratinocyte proliferation was stimulated by PRP. The in vitro scratch and transwell experiments revealed that PRP improved keratinocyte migration. In the MRSA-infected mouse skin model, PRP appeared to show a synergistic effect for wound area reduction by 39% when combined with β-lactams. The MRSA burden in the infected area was lessened two-fold after topical administration of the combined β-lactams and PRP. PRP inhibited macrophage infiltration in the wound site to shorten the inflammatory phase and accelerate the initiation of the proliferative phase. No skin irritation was detected with the topical delivery of this combination. Our findings suggested that β-lactams plus PRP was applicable to alleviate the problems associated with MRSA via dual antibacterial and regenerative activities.
耐药菌的出现促使人们开发新型抗感染治疗方法。本研究旨在评估富含血小板血浆（PRP）与β-内酰胺类抗生素（氨苄西林和/或苯唑西林）联合应用于耐甲氧西林金黄色葡萄球菌（MRSA）感染皮肤的抗菌和促进伤口愈合活性。PRP 从健康供体的外周血中采集。通过生长抑制曲线、集落形成单位（CFU）和 SYTO 9 检测评估抗 MRSA 活性。PRP 的掺入降低了氨苄西林和苯唑西林对 MRSA 的最低抑菌浓度（MIC）。β-内酰胺类抗生素与 PRP 联合使用可使 MRSA 的 CFU 减少三个对数级。根据蛋白质组学分析，PRP 消除 MRSA 的主要成分是补体系统和铁螯合蛋白。经含有β-内酰胺类抗生素和 PRP 的鸡尾酒处理后，微孔板上的黏附细菌菌落从 2.9×10 减少到 7.3×10 CFU。细胞研究表明 PRP 可刺激角质形成细胞增殖。体外划痕和 Transwell 实验表明 PRP 可促进角质形成细胞迁移。在 MRSA 感染的小鼠皮肤模型中，PRP 与β-内酰胺类抗生素联合应用时，可使伤口面积减少 39%，表现出协同作用。局部应用联合的β-内酰胺类抗生素和 PRP 可使感染区域的 MRSA 负荷减少两倍。PRP 抑制伤口部位巨噬细胞浸润，缩短炎症期并加速增殖期的启动。这种联合用药的局部给药未检测到皮肤刺激。我们的研究结果表明，β-内酰胺类抗生素加 PRP 通过双重抗菌和再生作用，可用于减轻与 MRSA 相关的问题。
