Jo Se Jin, Jiang Rui, Jung Sook In, Rhee Joon Haeng, Kim Young Ran
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Chonnam National University, 77 Youngbong-ro, Buk-gu, Gwangju, 61186, Republic of Korea.
Chonnam National University Medical School, Gwangju, 61469, Republic of Korea.
Sci Rep. 2025 Jul 3;15(1):23739. doi: 10.1038/s41598-025-09377-1.
Methicillin-resistant Staphylococcus aureus (MRSA) is a critical public health issue because of its resistance to multiple antibiotics, including β-lactams such as methicillin and oxacillin. To search for antibacterial sensitizers, we have investigated the synergistic antibacterial effects of the combination of the β-lactam antibiotic oxacillin and 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) against the MRSA strains. Checkerboard assays showed the synergistic antibacterial efficacy of NPPB combined with oxacillin against five MRSA strains. In addition, the combined effect of NPPB and oxacillin was evaluated by disc diffusion assay and time-dependent growth assay in MRSA strain ATCC 33591, and real-time PCR results showed that the combined treatment decreased the expression levels of abcA and norA genes encoding efflux transporters. NPPB also decreased the oxacillin-induced biofilm formation of ATCC 33591. Field emission transmission electron microscopy showed that the combination treatment induced extensive damage to the bacterial cell wall and membrane, leading to cell lysis. NPPB and oxacillin treated to mice for one week did not cause toxicity on the liver and kidney functions. These findings highlighted the potential of combination therapy of oxacillin and NPPB to treat MRSA infection by enhancing antibiotic efficacy and overcoming resistance.
耐甲氧西林金黄色葡萄球菌（MRSA）是一个严峻的公共卫生问题，因为它对多种抗生素具有耐药性，包括对甲氧西林和苯唑西林等β-内酰胺类抗生素耐药。为了寻找抗菌增敏剂，我们研究了β-内酰胺类抗生素苯唑西林与5-硝基-2-(3-苯丙基氨基)苯甲酸（NPPB）联合使用对MRSA菌株的协同抗菌作用。棋盘法试验表明NPPB与苯唑西林联合使用对五种MRSA菌株具有协同抗菌效果。此外，在MRSA菌株ATCC 33,591中通过纸片扩散法和时间依赖性生长试验评估了NPPB和苯唑西林的联合作用，实时PCR结果表明联合治疗降低了编码外排转运蛋白的abcA和norA基因的表达水平。NPPB还减少了ATCC 33,591中苯唑西林诱导的生物膜形成。场发射透射电子显微镜显示联合治疗对细菌细胞壁和细胞膜造成了广泛损伤，导致细胞裂解。用NPPB和苯唑西林对小鼠治疗一周未对其肝脏和肾脏功能造成毒性。这些发现突出了苯唑西林与NPPB联合治疗通过增强抗生素疗效和克服耐药性来治疗MRSA感染的潜力。
