Identification and treatment of the Staphylococcus aureus reservoir in vivo

• DOI: 10.1084/jem.20160334
• Publication Date: 2016-06-20T16:51:39Z
• Authors: Bas G.J. Surewaard; Justin F. Deniset; Franz J. Zemp; Matthias Amrein; Michael Otto; John Conly; Abdelwahab Omri; Robin M. Yates; Paul Kubes
• Keywords: Identification

Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is reaching epidemic proportions causing morbidity, mortality, and chronic disease due to relapses, suggesting an intracellular reservoir. Using spinning-disk confocal intravital microscopy track MRSA-GFP in vivo, we identified that within minutes after intravenous infection MRSA primarily sequestered killed by intravascular Kupffer cells (KCs) the liver. However, a minority of Staphylococci overcome KC's antimicrobial defenses. These bacteria survive proliferate for many days this niche, where they remain undetected recruited neutrophils. Over time, KCs lyse, releasing into circulation, enabling dissemination other organs such as kidneys. Vancomycin, antibiotic choice treat bacteremia, could not penetrate eradicate MRSA. based on location these specific macrophages, designed liposomal formulation vancomycin efficiently taken up diminished Targeting source reservoir dramatically protected liver but also organs, prevented mortality. This strategy help patients with Staphylococcal without need novel antibiotics targeting previously inaccessible KCs.