A study of 49 patients reveals that toxins from the bacterial pathogen Staphylococcus aureus can destroy the body's blood-clotting platelets, raising the risk of death during bacterial blood infections. Further experiments in mice also showed that the approved drugs ticagrelor and oseltamivir protected platelets and helped treat infections, suggesting these compounds could be repurposed into badly needed therapies for blood infections. Bacterial blood infections have mortality rates as high as 20% to 30% even with supportive care, and these rates have remained high for decades. Blood infections can also cause complications such as sepsis and endocarditis, and the rise of multidrug resistance has only compounded what was already a serious threat to public health. Infections with S. aureus are particularly difficult to treat, as the bacteria possess a range of tricks and defense mechanisms that allow them to evade or resist immune cells and antibiotics. While studying 49 patients with S. aureus blood infections, Josh Sun and colleagues discovered that many patients who succumbed showed abnormally low counts of platelets - small blood-clotting cells that can also combat infections. Follow-up experiments showed that S. aureus targeted platelets by secreting a toxin that destroyed platelet proteins, and by accelerating the clearance of platelets through the Ashwell-Morell receptor on liver cells. However, the approved blood thinner ticagrelor and the flu antiviral oseltamivir both protected platelets from the toxin-induced clearance in mice with S. aureus blood infections and improved survival. Sun et al. speculate that these drugs, if repurposed, could be combined with platelet infusions to further restore and protect platelet counts in ailing patients.
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Journal
Science Translational Medicine