PDF(Pubmed)
Abstract：
Methicillin-resistant Staphylococcus aureus (MRSA) has evolved into a dangerous pathogen resistant to beta-lactam antibiotics (BLAs) and has become a worrisome superbug. In this study, a strategy in which shikimic acid (SA), which has anti-inflammatory and antibacterial activity, is combined with BLAs to restart BLA activity was proposed for MRSA treatment. The synergistic effects of oxacillin combined with SA against oxacillin resistance in vitro and in vivo were investigated. The excellent synergistic effect of the oxacillin and SA combination was confirmed by performing the checkerboard assay, time-killing assay, live/dead bacterial cell viability assay, and assessing protein leakage. SEM showed that the cells in the control group had a regular, smooth, and intact surface. In contrast, oxacillin and SA or the combination treatment group exhibited different degrees of surface collapse. q-PCR indicated that the combination treatment group significantly inhibited the expression of the mecA gene. In vivo, we showed that the combination treatment increased the survival rate and decreased the bacterial load in mice. These results suggest that the combination of oxacillin with SA is considered an effective treatment option for MRSA, and the combination of SA with oxacillin in the treatment of MRSA is a novel strategy.
摘要：
耐甲氧西林金黄色葡萄球菌（MRSA）已演变成对β-内酰胺抗生素（BLA）具有抗性的危险病原体，并已成为令人担忧的超级细菌。在这项研究中,一种策略，其中莽草酸(SA)，具有抗炎和抗菌活性，与BLA联合重新启动BLA活性被提议用于MRSA治疗。研究了苯唑西林联合SA在体外和体内抗苯唑西林耐药性的协同作用。苯唑西林和SA组合的优异的协同作用通过进行棋盘试验得到证实。计时分析，活/死细菌细胞活力测定，并评估蛋白质渗漏。SEM显示,对照组细胞具有规律性,光滑,和完整的表面。相比之下,苯唑西林和SA或联合治疗组表现出不同程度的表面塌陷。q-PCR表明组合处理组显著抑制mecA基因的表达。在体内,我们表明，联合治疗提高了小鼠的存活率，降低了细菌负荷。这些结果表明，苯唑西林与SA的组合被认为是MRSA的有效治疗选择。SA与苯唑西林联合治疗MRSA是一种新的策略。
