Su Yu-Bin, Tang Xi-Kang, Zhu Ling-Ping, Yang Ke-Xin, Pan Li, Li Hui, Chen Zhuang-Gui
Department of Pediatrics and Department of Allergy, The Third Affiliated Hospital, State Key Laboratory of Bio-Control, Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai), Sun Yat-sen University, Guangzhou, China.
Department of Cell Biology, Ministry of Education Key Laboratory of Tumor Molecular Biology, Guangdong Provincial Key Laboratory of Bioengineering Medicine, Institute of Biomedicine, National Engineering Research Center of Genetic Medicine, College of Life Science and Technology, Jinan University, Guangzhou, China.
Front Microbiol. 2022 Apr 25;13:845173. doi: 10.3389/fmicb.2022.845173. eCollection 2022.
Antibiotic-resistant is insensitive to antibiotics and difficult to deal with. An understanding of the resistance mechanisms is required for the control of the pathogen. In this study, gas chromatography-mass spectrometer (GC-MS)-based metabolomics was performed to identify differential metabolomes in ciprofloxacin (CIP)-resistant strains that originated from ATCC 27853 and had minimum inhibitory concentrations (MICs) that were 16-, 64-, and 128-fold (PA-R16, PA-R64, and PA-R128, respectively) higher than the original value, compared to CIP-sensitive (PA-S). Upregulation of fatty acid biosynthesis forms a characteristic feature of the CIP-resistant metabolomes and fatty acid metabolome, which was supported by elevated gene expression and enzymatic activity in the metabolic pathway. The fatty acid synthase inhibitor triclosan potentiates CIP to kill PA-R128 and clinically multidrug-resistant strains. The potentiated killing was companied with reduced gene expression and enzymatic activity and the returned abundance of fatty acids in the metabolic pathway. Consistently, membrane permeability was reduced in the PA-R and clinically multidrug-resistant strains, which were reverted by triclosan. Triclosan also stimulated the uptake of CIP. These findings highlight the importance of the elevated biosynthesis of fatty acids in the CIP resistance of and provide a target pathway for combating CIP-resistant .
耐抗生素菌对抗生素不敏感且难以应对。为了控制病原体，需要了解其耐药机制。在本研究中，采用基于气相色谱 - 质谱联用仪（GC - MS）的代谢组学方法，以鉴定源自ATCC 27853的环丙沙星（CIP）耐药菌株中的差异代谢组，这些耐药菌株的最低抑菌浓度（MIC）分别比原始值高16倍、64倍和128倍（分别为PA - R16、PA - R64和PA - R128），并与CIP敏感菌株（PA - S）进行比较。脂肪酸生物合成的上调形成了CIP耐药代谢组和脂肪酸代谢组的特征，这在代谢途径中基因表达升高和酶活性增强方面得到了支持。脂肪酸合酶抑制剂三氯生增强了CIP对PA - R128和临床多重耐药菌株的杀伤作用。增强的杀伤作用伴随着代谢途径中基因表达和酶活性的降低以及脂肪酸丰度的恢复。一致地，PA - R和临床多重耐药菌株的膜通透性降低，而三氯生可使其恢复。三氯生还刺激了CIP的摄取。这些发现突出了脂肪酸生物合成增加在铜绿假单胞菌对CIP耐药中的重要性，并为对抗CIP耐药的铜绿假单胞菌提供了一个目标途径。
