title: Untargeted metabolomic profiling of amphenicol-resistant Campylobacter jejuni by ultra-high-performance liquid chromatography-mass spectrometry.
abstract: Campylobacter jejuni, an important foodborne microorganism, poses severe and emergent threats to human health as antibiotic resistance becomes increasingly prevalent. The mechanisms of drug resistance are hard to decipher, and little is known at the metabolic level. Here we apply metabolomic profiling to discover metabolic changes associated with amphenicol (chloramphenicol and florfenicol) resistance mutations of Campylobacter jejuni. An optimized sample preparation method was combined with ultra-high-performance liquid chromatography-time-of-flight mass spectrometry (UHPLC-TOF/MS) and pattern recognition for the analysis of small-molecule biomarkers of drug resistance. UHPLC-triple quadrupole MS operated in multiple reaction monitoring mode was used for quantitative analysis of metabolic features from UHPLC-TOF/MS profiling. Up to 41 differential metabolites involved in glycerophospholipid metabolism, sphingolipid metabolism, and fatty acid metabolism were observed in a chloramphenicol-resistant mutant strain of Campylobacter jejuni. A panel of 40 features was identified in florfenicol-resistant mutants, demonstrating changes in glycerophospholipid metabolism, sphingolipid metabolism, and tryptophan metabolism. This study shows that the UHPLC-MS-based metabolomics platform is a promising and valuable tool to generate new insights into the drug-resistant mechanism of Campylobacter jejuni.
authors.affiliation: Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University , Beijing 100193, P. R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Xi
authors.initials: X
authors.lastname: Xia
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Li
authors.forename: Gaowa
authors.initials: G
authors.lastname: Naren
authors.forename: Qin
authors.initials: Q
authors.lastname: Fu
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Congming
authors.initials: C
authors.lastname: Wu
authors.forename: Shuangyang
authors.initials: S
authors.lastname: Ding
authors.forename: Suxia
authors.initials: S
authors.lastname: Zhang
authors.forename: Haiyang
authors.initials: H
authors.lastname: Jiang
authors.forename: Jiancheng
authors.initials: J
authors.lastname: Li
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Shen
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D016123:Campylobacter jejuni / Q000187:drug effects* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D024881:Drug Resistance, Bacterial; D055432:Metabolomics; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D000900:Anti-Bacterial Agents
keywords: Campylobacter jejuni; UHPLC−MS; antibiotic resistance; glycerophospholipid metabolism; metabolomic