IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v9y2018i1d10.1038_s41467-018-03325-6.html
   My bibliography  Save this article

A macromolecular approach to eradicate multidrug resistant bacterial infections while mitigating drug resistance onset

Author

Listed:
  • Willy Chin

    (Institute of Bioengineering and Nanotechnology
    NUS Graduate School for Integrative Sciences and Engineering (NGS))

  • Guansheng Zhong

    (Zhejiang University)

  • Qinqin Pu

    (University of North Dakota)

  • Chuan Yang

    (Institute of Bioengineering and Nanotechnology)

  • Weiyang Lou

    (Zhejiang University)

  • Paola Florez De Sessions

    (Genome Institute of Singapore)

  • Balamurugan Periaswamy

    (Genome Institute of Singapore)

  • Ashlynn Lee

    (Institute of Bioengineering and Nanotechnology)

  • Zhen Chang Liang

    (Institute of Bioengineering and Nanotechnology)

  • Xin Ding

    (Institute of Bioengineering and Nanotechnology)

  • Shujun Gao

    (Institute of Bioengineering and Nanotechnology)

  • Collins Wenhan Chu

    (Genome Institute of Singapore)

  • Simone Bianco

    (IBM Almaden Research Center)

  • Chang Bao

    (Zhejiang University)

  • Yen Wah Tong

    (National University of Singapore)

  • Weimin Fan

    (Zhejiang University)

  • Min Wu

    (University of North Dakota)

  • James L. Hedrick

    (IBM Almaden Research Center)

  • Yi Yan Yang

    (Institute of Bioengineering and Nanotechnology)

Abstract

Polymyxins remain the last line treatment for multidrug-resistant (MDR) infections. As polymyxins resistance emerges, there is an urgent need to develop effective antimicrobial agents capable of mitigating MDR. Here, we report biodegradable guanidinium-functionalized polycarbonates with a distinctive mechanism that does not induce drug resistance. Unlike conventional antibiotics, repeated use of the polymers does not lead to drug resistance. Transcriptomic analysis of bacteria further supports development of resistance to antibiotics but not to the macromolecules after 30 treatments. Importantly, high in vivo treatment efficacy of the macromolecules is achieved in MDR A. baumannii-, E. coli-, K. pneumoniae-, methicillin-resistant S. aureus-, cecal ligation and puncture-induced polymicrobial peritonitis, and P. aeruginosa lung infection mouse models while remaining non-toxic (e.g., therapeutic index—ED50/LD50: 1473 for A. baumannii infection). These biodegradable synthetic macromolecules have been demonstrated to have broad spectrum in vivo antimicrobial activity, and have excellent potential as systemic antimicrobials against MDR infections.

Suggested Citation

  • Willy Chin & Guansheng Zhong & Qinqin Pu & Chuan Yang & Weiyang Lou & Paola Florez De Sessions & Balamurugan Periaswamy & Ashlynn Lee & Zhen Chang Liang & Xin Ding & Shujun Gao & Collins Wenhan Chu & , 2018. "A macromolecular approach to eradicate multidrug resistant bacterial infections while mitigating drug resistance onset," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03325-6
    DOI: 10.1038/s41467-018-03325-6
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-018-03325-6
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-018-03325-6?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Tianyu Wu & Min Zhou & Jingcheng Zou & Qi Chen & Feng Qian & Jürgen Kurths & Runhui Liu & Yang Tang, 2024. "AI-guided few-shot inverse design of HDP-mimicking polymers against drug-resistant bacteria," Nature Communications, Nature, vol. 15(1), pages 1-22, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03325-6. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.