Department of Chemistry and Biochemistry, Miami University, 651 E High St., Oxford, OH, 45056, USA.
Microb Biotechnol. 2017 Nov;10(6):1764-1774. doi: 10.1111/1751-7915.12839. Epub 2017 Aug 16.
It is known that changes in bacterial metabolism can contribute to the modulation of bacterial susceptibility to antibiotics. Understanding how bacterial metabolism is impacted by antibiotics may improve our understanding of the antibiotic mechanism of actions from a metabolic perspective. Here, we utilized a mass spectrometry-based targeted metabolic profiling technique to characterize the metabolome of a pair of isogenic methicillin-susceptible and resistant Staphylococcus aureus (MSSA and MRSA) strains RN450 and 450M treated with the sublethal dose of three antibiotics from different classes (β-lactams, aminoglycosides and quinolones). These treatments induced a set of metabolic alterations after 6 h of co-incubation with antibiotics. Similar and divergent metabolic perturbations were observed from different antibiotics to the tested strains. Different metabolic response from MSSA and MRSA to the same antibiotics was also detected in the study and indicated the potentially different stress response mechanism in MSSA and MRSA metabolism. This work has shown that a complex set of metabolic changes can be induced by a variety of antibiotics, and the comparative metabolomics strategy can provide a good understanding of this process from a metabolic perspective.
已知细菌代谢的变化可以影响其对抗生素的敏感性。从代谢角度理解抗生素如何影响细菌代谢，可能有助于我们更好地理解抗生素的作用机制。在这里，我们利用基于质谱的靶向代谢组学技术，对一对具有相同遗传背景的耐甲氧西林金黄色葡萄球菌（MSSA 和 MRSA）菌株 RN450 和 450M 进行了表型分析，这两株菌分别用三种不同类别的抗生素（β-内酰胺类、氨基糖苷类和喹诺酮类）的亚致死剂量处理。这些处理在与抗生素共孵育 6 小时后诱导了一组代谢改变。不同抗生素对测试菌株的代谢干扰存在相似和不同之处。本研究还检测到 MSSA 和 MRSA 对相同抗生素的不同代谢反应，表明 MSSA 和 MRSA 代谢中可能存在不同的应激反应机制。这项工作表明，多种抗生素可以诱导一系列复杂的代谢变化，比较代谢组学策略可以从代谢角度很好地理解这一过程。
