| Summary: | <i>Staphylococcus aureus</i> (<i>S. aureus</i>) infections are a major healthcare challenge and new treatment alternatives are needed. <i>S. aureus</i> septic arthritis, a debilitating joint disease, causes permanent joint dysfunction in almost 50% of the patients. <i>S. aureus</i> bacteremia is associated with higher mortalities than bacteremia caused by most other microbes and can develop to severe sepsis and death. The key to new therapies is understanding the interplay between bacterial virulence factors and host immune response, which decides the disease outcome. <i>S. aureus</i> produces numerous virulence factors that facilitate bacterial dissemination, invasion into joint cavity, and cause septic arthritis. Monocytes, activated by several components of <i>S. aureus</i> such as lipoproteins, are responsible for bone destructions. In <i>S. aureus</i> sepsis, cytokine storm induced by <i>S. aureus</i> components leads to the hyperinflammatory status, DIC, multiple organ failure, and later death. The immune suppressive therapies at the very early time point might be protective. However, the timing of treatment is crucial, as late treatment may aggravate the immune paralysis and lead to uncontrolled infection and death.
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