Identification and treatment of the Staphylococcus aureus reservoir in vivo

Abstract

Kubes et al. show that methicillin-resistant Staphylococcus aureus (MRSA) survive and proliferate inside Kupffer cells. Intracellular MRSA is resistant to neutrophil-killing and antibiotics treatment and, when released into the circulation, can infect other organs.

α-Toxin Induces Platelet Aggregation and Liver Injury during Staphylococcus aureus Sepsis

“…S. aureus required 4–8 h to secrete sufficient AT, as AT-dependent platelet aggregation was only observed at 8 h while direct administration of AT caused instantaneous aggregation. Remarkably, this timeframe coincided directly with the time it takes for S. aureus to escape from Kupffer cells (Surewaard et al, 2016). Blocking AT reduced the staphylococcal burden inside the liver as well as the kidney.…”

“…We previously reported that some S. aureus survive and even replicate inside Kupffer cells and subsequently disseminate to kidneys (Surewaard et al, 2016). S. aureusΔhla did not survive as effectively inside the liver as the WT strain (Figure 5C) and dissemination to kidneys trended towards a lower bacterial burden (Figure 5D).…”

“…Our previous work suggested that 90% of bacteria were killed in Kupffer cells, however 10% of the S. aureus inside the macrophage overcame the phagocytic machinery, and lysed the macrophage leading to bacterial dissemination (Surewaard et al, 2016). MEDI4893*prophylaxis, did not affect uptake of the S. aureus consistent with the view that AT is secreted and not displayed on the staphylococcal surface AND in line with previous reports that MEDI4893* has no opsonophagocytic properties (Tkaczyk et al, 2016; Tkaczyk et al, 2017).…”

Staphylococcus aureus pore-forming toxins: The interface of pathogen and host complexity

“…A recent study found that S. aureus that survive within phagocytes serve as a reservoir of infection during systemic disease, resulting in increased bacterial outgrowth and reduced host survival [183]. Hla- induced changes in intracellular signaling causes increased β1-integrin surface expression and subsequent phagocytosis, allowing bacteria to escape the extracellular-bactericidal functions of mast cells [184, 185].…”

Bispecific antibody targets multiple Pseudomonas aeruginosa evasion mechanisms in the lung vasculature

“…For liver imaging, mice were anesthetized and cannulated as described above, and intravital imaging was performed as previously described (19,20).…”