| Literature DB >> 26536114 |
Sophie M Lehar1, Thomas Pillow2, Min Xu3, Leanna Staben2, Kimberly K Kajihara1, Richard Vandlen4, Laura DePalatis4, Helga Raab4, Wouter L Hazenbos1, J Hiroshi Morisaki1, Janice Kim3, Summer Park3, Martine Darwish4, Byoung-Chul Lee4, Hilda Hernandez5, Kelly M Loyet5, Patrick Lupardus6, Rina Fong6, Donghong Yan3, Cecile Chalouni7, Elizabeth Luis4, Yana Khalfin5, Emile Plise8, Jonathan Cheong8, Joseph P Lyssikatos2, Magnus Strandh9, Klaus Koefoed9, Peter S Andersen9, John A Flygare2, Man Wah Tan1, Eric J Brown1, Sanjeev Mariathasan1.
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.Entities:
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Year: 2015 PMID： 26536114 DOI： 10.1038/nature16057
Source DB: PubMed Journal: Nature ISSN： 0028-0836 Impact factor: 49.962