The combined antibacterial effects of sodium new houttuyfonate and berberine chloride against growing and persistent met
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RESEARCH ARTICLE
Open Access
The combined antibacterial effects of sodium new houttuyfonate and berberine chloride against growing and persistent methicillin-resistant and vancomycinintermediate Staphylococcus aureus Xue Li1, Penghe Wang1,2, Xinxin Hu1, Youwen Zhang1, Xi Lu1, Congran Li1, Tongying Nie1, Guoqing Li1, Xiukun Wang1, Jing Pang1, Yun Lu1, Xinyi Yang1* and Xuefu You1*
Abstract Background: Infections caused by drug-resistant Staphylococcus aureus, especially vancomycin-intermediate Staphylococcus aureus (VISA), leave clinicians with limited therapeutic options for treatment. Persister cells is a leading cause of recalcitrant infection and antibiotic treatment failure, and there is no drug in clinical use that specifically targets persister cells currently. Here, we report a promising combination therapy of sodium new houttuyfonate (SNH) and berberine chloride (BBR) which is able to eradicate both growing and persistent drugresistant Staphylococcus aureus. Results: The susceptibility test showed SNH exhibited anti-MRSA activity with MIC90 at 64 μg/mL, while BBR showed weak anti-MRSA activity with MIC90 at 512 μg/mL. MICs of BBR in combination with 1/2 MIC SNH decreased by 4 to 64 folds compared with MICs of BBR alone. The results of time-killing assays revealed that the combined use of sub-MIC SNH and BBR offered an in vitro synergistic action against growing MRSA (including pathogenic MRSA) and VISA strains. More importantly, the combination of SNH and BBR was able to eradicate VISA Mu50 and pathogenic MRSA persister cells. The synergistic effect is likely related to the interruption of the cell membrane caused by SNH, which is confirmed by scanning electron microscope and membrane potential and permeability analysis. Conclusions: Our study provide a promising clinical curative strategy for combating drug-resistant S. aureus infections, especially for recalcitrant infections caused by persister cells. Keywords: Combination therapy, Berberine, Sodium new houttuyfonate, Persistence, MRSA, VISA
* Correspondence: [email protected]; [email protected] 1 Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted
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