Department of Chemistry and Biochemistry, Miami University, Oxford, OH, 45056, USA.
Department of Chemistry and Biochemistry, Miami University, Oxford, OH, 45056, USA; Department of Human Sciences, The Ohio State University, Columbus, OH, 43210, USA.
J Pharm Biomed Anal. 2019 Apr 15;167:140-148. doi: 10.1016/j.jpba.2019.02.010. Epub 2019 Feb 8.
Traditional strategies in developing novel drugs to treat antibiotic-resistant S. aureus have not been very successful to date, therefore, there is an urgent need for creative usage of existing agents that can treat and control S. aureus infection. This study demonstrated that a combination of glucose and a sublethal dose of antibiotic can reduce the survivability of S. aureus in a glucose concentration-dependent manner. Mass spectrometry-based targeted metabolic profiling detected massive metabolic profile shift of both methicillin-susceptible and resistant S. aureus after methicillin and glucose co-treatment. The dramatic alteration of metabolites from these metabolic pathways can be detected when 10 mg/L or higher concentration of glucose were added to methicillin treated culture. Our data also indicated that multiple biochemical metabolic pathways, including pyrimidine metabolism and valine, leucine, and isoleucine degradation showed a significant difference (p < 0.01) in comparison of control groups to glucose treatment groups. Taken together, this pilot study suggested that exogenous glucose in combination with a sublethal dose of antibiotics can disturb the metabolism of both methicillin-susceptible and resistant S. aureus, and enhance the antibiotic bactericidal effect.
传统的开发新型抗生素耐药性金黄色葡萄球菌药物的策略迄今尚未取得很大成功，因此，迫切需要创造性地利用现有药物来治疗和控制金黄色葡萄球菌感染。本研究表明，葡萄糖和亚致死剂量抗生素的联合使用可以降低金黄色葡萄球菌在葡萄糖浓度依赖性方式下的存活能力。基于质谱的靶向代谢组学检测到耐甲氧西林和敏感金黄色葡萄球菌在甲氧西林和葡萄糖共同处理后发生了大量的代谢谱变化。当向甲氧西林处理的培养物中加入 10mg/L 或更高浓度的葡萄糖时，可以检测到这些代谢途径中代谢物的显著变化。我们的数据还表明，与对照组相比，包括嘧啶代谢和缬氨酸、亮氨酸和异亮氨酸降解在内的多个生化代谢途径在葡萄糖处理组中表现出显著差异（p<0.01）。综上所述，这项初步研究表明，外源性葡萄糖与亚致死剂量抗生素联合使用可以扰乱耐甲氧西林和敏感金黄色葡萄球菌的代谢，并增强抗生素的杀菌作用。
