Platelet activation by a relapsing fever spirochaete results in enhanced bacterium-platelet interaction via integrin alpha(IIb)beta(3) activation

Borrelia hermsii, a spirochaete responsible for relapsing fever in humans, grows to high density in the bloodstream and causes thrombocytopenia. We sh ow here that B. hermsii binds to human platelets. Extended culture in bacte riological medium resulted in both diminished infectivity in vivo and dimin ished platelet binding in vitro. Platelet binding was promoted by the plate let integrin alpha (IIb)beta (3): the bacterium bound to purified integrin alpha (IIb)beta (3), and bacterial binding to platelets was diminished by a lpha (IIb)beta (3) antagonists or by a genetic defect in this integrin. Int egrin alpha (IIb)beta (3) undergoes a conformational change upon platelet a ctivation, and bacteria bound more efficiently to activated rather than res ting platelets. Nevertheless, B. hermsii bound at detectable levels to prep arations of resting platelets. The bacterium did not recognize a point muta nt of alpha (IIb)beta (3) that cannot acquire an active conformation. Rathe r, B. hermsii was capable of triggering platelet and integrin alpha (IIb)be ta (3) activation, as indicated by the expression of the platelet activatio n marker P-selectin and integrin alpha (IIb)beta (3) in its active conforma tion. The degree of platelet activation varied depending upon bacterial str ain and growth conditions. Prostacyclin I-2, an inhibitor of platelet activ ation, diminished bacterial attachment, indicating that activation enhanced bacterial binding. Thus, B. hermsii signals the host cell to activate a cr itical receptor for the bacterium, thereby promoting high-level bacterial a ttachment.