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. 2015 Nov 19;527(7578):323-8.
doi: 10.1038/nature16057. Epub 2015 Nov 4.

Novel antibody-antibiotic conjugate eliminates intracellular S. aureus

Sophie M Lehar  1 , Thomas Pillow  2 , Min Xu  3 , Leanna Staben  2 , Kimberly K Kajihara  1 , Richard Vandlen  4 , Laura DePalatis  4 , Helga Raab  4 , Wouter L Hazenbos  1 , J Hiroshi Morisaki  1 , Janice Kim  3 , Summer Park  3 , Martine Darwish  4 , Byoung-Chul Lee  4 , Hilda Hernandez  5 , Kelly M Loyet  5 , Patrick Lupardus  6 , Rina Fong  6 , Donghong Yan  3 , Cecile Chalouni  7 , Elizabeth Luis  4 , Yana Khalfin  5 , Emile Plise  8 , Jonathan Cheong  8 , Joseph P Lyssikatos  2 , Magnus Strandh  9 , Klaus Koefoed  9 , Peter S Andersen  9 , John A Flygare  2 , Man Wah Tan  1 , Eric J Brown  1 , Sanjeev Mariathasan  1
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Novel antibody-antibiotic conjugate eliminates intracellular S. aureus

Sophie M Lehar et al. Nature. .

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.

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