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Journal of Microbiology

, Volume 57, Issue 5, pp 405–412 | Cite as

Expansion of antibacterial spectrum of xanthorrhizol against Gram-negatives in combination with PMBN and food-grade antimicrobials

  • Man Su Kim
  • Ha-Rim Kim
  • Haebom Kim
  • Soo-Keun Choi
  • Chang-Hwan Kim
  • Jae-Kwan Hwang
  • Seung-Hwan ParkEmail author
Article

Abstract

Xanthorrhizol (XTZ), isolated from Curcuma xanthorrhiza, has potent antifungal and antibacterial activity. It shows very strong activity against Gram-positive bacteria, such as Streptococcus mutans and Staphylococcus aureus, but is generally not active against Gram-negative bacteria. In this study, we explored the possibility of using a combination strategy for expanding the antimicrobial spectrum of XTZ against Gram-negative bacteria. To take advantage of XTZ being a food-grade material, 10 food-grade or generally recognized as safe (GRAS) antimicrobial compounds with low toxicities were selected for combination therapy. In addition, polymyxin B nonapeptide (PMBN), which is less toxic than polymyxin B, was also selected as an outer membrane permeabilizer. The antibacterial activity of various double or triple combinations with or without XTZ were assayed in vitro against four Gram-negative bacterial species (Escherichia coli, Salmonella enterica serovar Typhi, Salmonella enterica serovar Typhimurium, and Vibrio cholerae), with synergistic combinations exhibiting clear activity subjected to further screening. The combinations with the greatest synergism were XTZ + PMBN + nisin, XTZ + PMBN + carvacrol, and XTZ + PMBN + thymol. These combinations also showed potent antimicrobial activity against Shigella spp., Yersinia enterocolitica, and Acinetobacter baumannii. In time-kill assays, the three combinations achieved complete killing of E. coli within 2 h, and S. Typhi and V. cholera within 15 min. This is the first report on expanding the activity spectrum of XTZ against Gram-negative bacteria through combination with PMBN and food-grade or GRAS substances, with the resulting findings being particularly useful for increasing the industrial and medical applications of XTZ.

Keywords

xanthorrhizol PMBN carvacrol thymol nisin combination synergistic effect 

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Copyright information

© The Microbiological Society of Korea 2019

Authors and Affiliations

  • Man Su Kim
    • 1
    • 2
  • Ha-Rim Kim
    • 1
  • Haebom Kim
    • 3
  • Soo-Keun Choi
    • 1
    • 2
  • Chang-Hwan Kim
    • 4
  • Jae-Kwan Hwang
    • 3
  • Seung-Hwan Park
    • 1
    • 2
    Email author
  1. 1.Infectious Disease Research CenterKorea Research Institute of Bioscience and Biotechnology (KRIBB)DaejeonRepublic of Korea
  2. 2.Department of Biosystems and Bioengineering, KRIBB School of BiotechnologyUniversity of Science and Technology (UST)DaejeonRepublic of Korea
  3. 3.Department of BiotechnologyYonsei UniversitySeoulRepublic of Korea
  4. 4.The 5th R&D InstituteAgency for Defense Development (ADD)DaejeonRepublic of Korea

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