title: Human Lysozyme Synergistically Enhances Bactericidal Dynamics and Lowers the Resistant Mutant Prevention Concentration for Metronidazole to Helicobacter pylori by Increasing Cell Permeability.
abstract: Metronidazole (MNZ) is an effective agent that has been employed to eradicateHelicobacter pylori(H. pylori). The emergence of broad MNZ resistance inH. pylorihas affected the efficacy of this therapeutic agent. The concentration of MNZ, especially the mutant prevention concentration (MPC), plays an important role in selecting or enriching resistant mutants and regulating therapeutic effects. A strategy to reduce the MPC that can not only effectively treatH. pyloribut also prevent resistance mutations is needed.H. pyloriis highly resistant to lysozyme. Lysozyme possesses a hydrolytic bacterial cell wall peptidoglycan and a cationic dependent mode. These effects can increase the permeability of bacterial cells and promote antibiotic absorption into bacterial cells. In this study, human lysozyme (hLYS) was used to probe its effects on the integrity of theH. pyloriouter and inner membranes using as fluorescent probe hydrophobic 1-N-phenyl-naphthylamine (NPN) and the release of aspartate aminotransferase. Further studies using a propidium iodide staining method assessed whether hLYS could increase cell permeability and promote cell absorption. Finally, we determined the effects of hLYS on the bactericidal dynamics and MPC of MNZ inH. pylori. Our findings indicate that hLYS could dramatically increase cell permeability, reduce the MPC of MNZ forH. pylori, and enhance its bactericidal dynamic activity, demonstrating that hLYS could reduce the probability of MNZ inducing resistance mutations.
authors: The Department of Pharmacy, Food and Drug School, Anhui Science and Technology University, Fengyang 233100, China. zhangxiaolin8@126.com.
authors: Xiaolin
authors: X
authors: Zhang
authors: The School of Life Science, University of Science and Technology of China, Hefei 230032, China. SA12226011@mail.ustu.edu.cn.
authors: Anmin
authors: A
authors: Jiang
authors: The Department of Pharmacy, Food and Drug School, Anhui Science and Technology University, Fengyang 233100, China. yuh@ahstu.edu.cn.
authors: Hao
authors: H
authors: Yu
authors: The Department of Pharmacy, Food and Drug School, Anhui Science and Technology University, Fengyang 233100, China. xiongyy@ahstu.edu.cn.
authors: Youyi
authors: Y
authors: Xiong
authors: The Department of Pharmacy, Food and Drug School, Anhui Science and Technology University, Fengyang 233100, China. zhougl@ahstu.edu.cn.
authors: Guoliang
authors: G
authors: Zhou
authors: The Department of Pharmacy, Food and Drug School, Anhui Science and Technology University, Fengyang 233100, China. qinms@ahstu.edu.cn.
authors: Meisong
authors: M
authors: Qin
authors: The Department of Pharmacy, Food and Drug School, Anhui Science and Technology University, Fengyang 233100, China. doujf@ahstu.edu.cn.
authors: Jinfeng
authors: J
authors: Dou
authors: The Department of Pharmacy, Food and Drug School, Anhui Science and Technology University, Fengyang 233100, China. wangjf007@ahstu.edu.cn.|The Ministry of Agriculture Key Laboratory of Microbial Organic Fertilizer, Bengbu 233030, China. wangjf007@ahstu.edu.cn.
authors: Jianfei
authors: J
authors: Wang
mesh_terms: D015057:1-Naphthylamine / Q000031:analogs & derivatives / Q000378:metabolism; D001219:Aspartate Aminotransferases; D002473:Cell Wall / Q000187:drug effects*; D024881:Drug Resistance, Bacterial / Q000187:drug effects*; D004357:Drug Synergism; D016480:Helicobacter pylori / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008795:Metronidazole / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D009113:Muramidase / Q000494:pharmacology*; D009154:Mutation
chemical_list: D008795:Metronidazole; C005444:N-phenyl-1-naphthylamine; D015057:1-Naphthylamine; D001219:Aspartate Aminotransferases; D009113:Muramidase; C514728:lysozyme C, human
keywords: H. pylori; bactericidal dynamics; human lysozyme; metronidazole; mutant prevention concentration