Novel antibody–antibiotic conjugate eliminates intracellular S. aureus

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, Martine Darwish, Byoung-Chul Lee, Hilda Hernandez, Kelly M. Loyet, Patrick Lupardus, Rina Fong, Donghong Yan, Cecile Chalouni, Elizabeth Luis, Yana Khalfin, Emile Plise, Jonathan Cheong, Joseph P. Lyssikatos, Magnus Strandh, Klaus Koefoed, Peter S. Andersen, John A. Flygare, Man Wah Tan, Eric J. Brown () and Sanjeev Mariathasan ()
Additional contact information
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.

Nature, 2015, vol. 527, issue 7578, 323-328

Abstract: 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.

Date: 2015
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DOI: 10.1038/nature16057

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