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Novel antibody–antibiotic conjugate eliminates intracellular S. aureus

Author

Listed:
  • Sophie M. Lehar

    (Genentech Inc.)

  • Thomas Pillow

    (Genentech Inc.)

  • Min Xu

    (Genentech Inc.)

  • Leanna Staben

    (Genentech Inc.)

  • Kimberly K. Kajihara

    (Genentech Inc.)

  • Richard Vandlen

    (Genentech Inc.)

  • Laura DePalatis

    (Genentech Inc.)

  • Helga Raab

    (Genentech Inc.)

  • Wouter L. Hazenbos

    (Genentech Inc.)

  • J. Hiroshi Morisaki

    (Genentech Inc.)

  • Janice Kim

    (Genentech Inc.)

  • Summer Park

    (Genentech Inc.)

  • Martine Darwish

    (Genentech Inc.)

  • Byoung-Chul Lee

    (Genentech Inc.)

  • Hilda Hernandez

    (Genentech Inc.)

  • Kelly M. Loyet

    (Genentech Inc.)

  • Patrick Lupardus

    (Genentech Inc.)

  • Rina Fong

    (Genentech Inc.)

  • Donghong Yan

    (Genentech Inc.)

  • Cecile Chalouni

    (Genentech Inc.)

  • Elizabeth Luis

    (Genentech Inc.)

  • Yana Khalfin

    (Genentech Inc.)

  • Emile Plise

    (Genentech Inc.)

  • Jonathan Cheong

    (Genentech Inc.)

  • Joseph P. Lyssikatos

    (Genentech Inc.)

  • Magnus Strandh

    (Symphogen A/S)

  • Klaus Koefoed

    (Symphogen A/S)

  • Peter S. Andersen

    (Symphogen A/S)

  • John A. Flygare

    (Genentech Inc.)

  • Man Wah Tan

    (Genentech Inc.)

  • Eric J. Brown

    (Genentech Inc.)

  • Sanjeev Mariathasan

    (Genentech Inc.)

Abstract

Staphylococcus aureus is considered to be an extracellular pathogen. However, survival of S. aureus within host cells may provide a reservoir relatively protected from antibiotics, thus enabling long-term colonization of the host and explaining clinical failures and relapses after antibiotic therapy. Here we confirm that intracellular reservoirs of S. aureus in mice comprise a virulent subset of bacteria that can establish infection even in the presence of vancomycin, and we introduce a novel therapeutic that effectively kills intracellular S. aureus. This antibody–antibiotic conjugate consists of an anti-S. aureus antibody conjugated to a highly efficacious antibiotic that is activated only after it is released in the proteolytic environment of the phagolysosome. The antibody–antibiotic conjugate is superior to vancomycin for treatment of bacteraemia and provides direct evidence that intracellular S. aureus represents an important component of invasive infections.

Suggested Citation

  • Sophie M. Lehar & Thomas Pillow & Min Xu & Leanna Staben & Kimberly K. Kajihara & Richard Vandlen & Laura DePalatis & Helga Raab & Wouter L. Hazenbos & J. Hiroshi Morisaki & Janice Kim & Summer Park &, 2015. "Novel antibody–antibiotic conjugate eliminates intracellular S. aureus," Nature, Nature, vol. 527(7578), pages 323-328, November.
    • Handle: RePEc:nat:nature:v:527:y:2015:i:7578:d:10.1038_nature16057
    DOI: 10.1038/nature16057
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    Cited by:

    1. Ines Rodrigues Lopes & Laura Maria Alcantara & Ricardo Jorge Silva & Jerome Josse & Elena Pedrero Vega & Ana Marina Cabrerizo & Melanie Bonhomme & Daniel Lopez & Frederic Laurent & Francois Vandenesch, 2022. "Microscopy-based phenotypic profiling of infection by Staphylococcus aureus clinical isolates reveals intracellular lifestyle as a prevalent feature," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    2. Xinghong Zhao & Xinyi Zhong & Shinong Yang & Jiarong Deng & Kai Deng & Zhengqun Huang & Yuanfeng Li & Zhongqiong Yin & Yong Liu & Jakob H. Viel & Hongping Wan, 2024. "Guiding antibiotics towards their target using bacteriophage proteins," Nature Communications, Nature, vol. 15(1), pages 1-17, December.

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