Novel antibody-antibiotic conjugate eliminates intracellular S. aureus
- Autores: Sophie M. Lehar, Thomas Pillow, Min Xu, Leanna Staben
- Localización: Nature: International weekly journal of science, ISSN 0028-0836, Vol. 527, Nº 7578, 2015, págs. 323-328
- Idioma: inglés
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Resumen
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.
