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Antibiotic-chemoattractants enhance neutrophil clearance of Staphylococcus aureus

Author

Listed:
  • Jennifer A. E. Payne

    (Monash University
    Monash University
    Monash University)

  • Julien Tailhades

    (Monash University
    Monash University
    Monash University)

  • Felix Ellett

    (Shriners Hospital for Children, and Harvard Medical School)

  • Xenia Kostoulias

    (Monash University)

  • Alex J. Fulcher

    (Monash University)

  • Ting Fu

    (Monash University)

  • Ryan Leung

    (Monash University)

  • Stephanie Louch

    (Monash University)

  • Amy Tran

    (Monash University)

  • Severin A. Weber

    (Monash University
    Monash University)

  • Ralf B. Schittenhelm

    (Monash University)

  • Graham J. Lieschke

    (Monash University)

  • Chengxue Helena Qin

    (Monash University
    Baker Heart and Diabetes Institute)

  • Daniel Irima

    (Shriners Hospital for Children, and Harvard Medical School)

  • Anton Y. Peleg

    (Monash University
    The Alfred Hospital
    Monash University)

  • Max J. Cryle

    (Monash University
    Monash University
    Monash University)

Abstract

The pathogen Staphylococcus aureus can readily develop antibiotic resistance and evade the human immune system, which is associated with reduced levels of neutrophil recruitment. Here, we present a class of antibacterial peptides with potential to act both as antibiotics and as neutrophil chemoattractants. The compounds, which we term ‘antibiotic-chemoattractants’, consist of a formylated peptide (known to act as chemoattractant for neutrophil recruitment) that is covalently linked to the antibiotic vancomycin (known to bind to the bacterial cell wall). We use a combination of in vitro assays, cellular assays, infection-on-a-chip and in vivo mouse models to show that the compounds improve the recruitment, engulfment and killing of S. aureus by neutrophils. Furthermore, optimizing the formyl peptide sequence can enhance neutrophil activity through differential activation of formyl peptide receptors. Thus, we propose antibiotic-chemoattractants as an alternate approach for antibiotic development.

Suggested Citation

  • Jennifer A. E. Payne & Julien Tailhades & Felix Ellett & Xenia Kostoulias & Alex J. Fulcher & Ting Fu & Ryan Leung & Stephanie Louch & Amy Tran & Severin A. Weber & Ralf B. Schittenhelm & Graham J. Li, 2021. "Antibiotic-chemoattractants enhance neutrophil clearance of Staphylococcus aureus," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26244-5
    DOI: 10.1038/s41467-021-26244-5
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    References listed on IDEAS

    as
    1. Cheng Xue Qin & Lauren T. May & Renming Li & Nga Cao & Sarah Rosli & Minh Deo & Amy E. Alexander & Duncan Horlock & Jane E. Bourke & Yuan H. Yang & Alastair G. Stewart & David M. Kaye & Xiao-Jun Du & , 2017. "Small-molecule-biased formyl peptide receptor agonist compound 17b protects against myocardial ischaemia-reperfusion injury in mice," Nature Communications, Nature, vol. 8(1), pages 1-13, April.
    2. Tong Chen & Muya Xiong & Xin Zong & Yunjun Ge & Hui Zhang & Mu Wang & Gye Won Han & Cuiying Yi & Limin Ma & Richard D. Ye & Yechun Xu & Qiang Zhao & Beili Wu, 2020. "Structural basis of ligand binding modes at the human formyl peptide receptor 2," Nature Communications, Nature, vol. 11(1), pages 1-9, December.
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