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Molecules 2016, 21(11), 1435; doi:10.3390/molecules21111435

Human Lysozyme Synergistically Enhances Bactericidal Dynamics and Lowers the Resistant Mutant Prevention Concentration for Metronidazole to Helicobacter pylori by Increasing Cell Permeability

1
The Department of Pharmacy, Food and Drug School, Anhui Science and Technology University, Fengyang 233100, China
2
The School of Life Science, University of Science and Technology of China, Hefei 230032, China
3
The Ministry of Agriculture Key Laboratory of Microbial Organic Fertilizer, Bengbu 233030, China
*
Authors to whom correspondence should be addressed.
Academic Editor: Derek J. McPhee
Received: 5 September 2016 / Revised: 25 October 2016 / Accepted: 25 October 2016 / Published: 28 October 2016
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Abstract

Metronidazole (MNZ) is an effective agent that has been employed to eradicate Helicobacter pylori (H. pylori). The emergence of broad MNZ resistance in H. pylori has 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 treat H. pylori but also prevent resistance mutations is needed. H. pylori is 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 the H. pylori outer 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 in H. pylori. Our findings indicate that hLYS could dramatically increase cell permeability, reduce the MPC of MNZ for H. pylori, and enhance its bactericidal dynamic activity, demonstrating that hLYS could reduce the probability of MNZ inducing resistance mutations. View Full-Text
Keywords: H. pylori; metronidazole; human lysozyme; mutant prevention concentration; bactericidal dynamics H. pylori; metronidazole; human lysozyme; mutant prevention concentration; bactericidal dynamics
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MDPI and ACS Style

Zhang, X.; Jiang, A.; Yu, H.; Xiong, Y.; Zhou, G.; Qin, M.; Dou, J.; Wang, J. Human Lysozyme Synergistically Enhances Bactericidal Dynamics and Lowers the Resistant Mutant Prevention Concentration for Metronidazole to Helicobacter pylori by Increasing Cell Permeability. Molecules 2016, 21, 1435.

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