title: Systematic and Molecular Basis of the Antibacterial Action of Quinoxaline 1,4-Di-N-Oxides against Escherichia coli.
abstract: Quinoxaline 1,4-di-N-oxides (QdNOs) are widely known as potent antibacterial agents, but their antibacterial mechanisms are incompletely understood. In this study, the transcriptomic and proteomic profiles of Escherichia coli exposed to QdNOs were integratively investigated, and the results demonstrated that QdNOs mainly induced an SOS response and oxidative stress. Moreover, genes and proteins involved in the bacterial metabolism, cellular structure maintenance, resistance and virulence were also found to be changed, conferring bacterial survival strategies. Biochemical assays showed that reactive oxygen species were induced in the QdNO-treated bacteria and that free radical scavengers attenuated the antibacterial action of QdNOs and DNA damage, suggesting an oxidative-DNA-damage action of QdNOs. The QdNO radical intermediates, likely carbon-centered and aryl-type radicals, as identified by electron paramagnetic resonance, were the major radicals induced by QdNOs, and xanthine oxidase was one of the QdNO-activating enzymes. This study provides new insights into the action of QdNOs in a systematic manner and increases the current knowledge of bacterial physiology under antibiotic stresses, which may be of great value in the development of new antibiotic-potentiating strategies.
authors: MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, Hubei, 430070, China; Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Huazhong Agricultural University, Wuhan, Hubei, 430070, China.
authors: Guyue
authors: G
authors: Cheng
authors: MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, Hubei, 430070, China.
authors: Bei
authors: B
authors: Li
authors: MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, Hubei, 430070, China.
authors: Chenxi
authors: C
authors: Wang
authors: MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, Hubei, 430070, China.
authors: Hongfei
authors: H
authors: Zhang
authors: MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, Hubei, 430070, China.
authors: Guixia
authors: G
authors: Liang
authors: MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, Hubei, 430070, China.
authors: Zhifei
authors: Z
authors: Weng
authors: MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, Hubei, 430070, China; Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Huazhong Agricultural University, Wuhan, Hubei, 430070, China.
authors: Haihong
authors: H
authors: Hao
authors: MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, Hubei, 430070, China; Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Huazhong Agricultural University, Wuhan, Hubei, 430070, China.
authors: Xu
authors: X
authors: Wang
authors: National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, Hubei, 430070, China; Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Huazhong Agricultural University, Wuhan, Hubei, 430070, China.
authors: Zhenli
authors: Z
authors: Liu
authors: MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, Hubei, 430070, China; Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Huazhong Agricultural University, Wuhan, Hubei, 430070, China.
authors: Menghong
authors: M
authors: Dai
authors: National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, Hubei, 430070, China; Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Huazhong Agricultural University, Wuhan, Hubei, 430070, China.
authors: Yulian
authors: Y
authors: Wang
authors: MOA Laboratory for Risk Assessment of Quality and Safety of Livestock and Poultry Products, Huazhong Agricultural University, Wuhan, Hubei, 430070, China; National Reference Laboratory of Veterinary Drug Residues (HZAU) and MAO Key Laboratory for Detection of Veterinary Drug Residues, Huazhong Agricultural University, Wuhan, Hubei, 430070, China; Hubei Collaborative Innovation Center for Animal Nutrition and Feed Safety, Huazhong Agricultural University, Wuhan, Hubei, 430070, China.
authors: Zonghui
authors: Z
authors: Yuan
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D008826:Microbial Sensitivity Tests; D058977:Molecular Sequence Annotation; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D014176:Protein Biosynthesis / Q000187:drug effects; D040901:Proteomics; D011810:Quinoxalines / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000819:agonists / Q000378:metabolism; D013014:SOS Response, Genetics / Q000187:drug effects; D013329:Structure-Activity Relationship; D000077704:Tirapazamine; D014227:Triazines / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; C545385:Mequindox; D011810:Quinoxalines; D017382:Reactive Oxygen Species; D014227:Triazines; D000077704:Tirapazamine; C020728:cyadox; C013168:olaquindox