Platelet activation by a relapsing fever spirochaete results in enhanced bacterium-platelet interaction via integrin αIIbβ3 activation

Borrelia hermsii, a spirochaete responsible for relapsing fever in humans, grows to high density in the bloodstream and causes thrombocytopenia. We show here that B. hermsii binds to human platelets. Extended culture in bacteriological medium resulted in both diminished infectivity in vivo and diminished platelet binding in vitro. Platelet binding was promoted by the platelet integrin alpha (IIb)beta (3): the bacterium bound to purified integrin alpha (IIb)beta (3), and bacterial binding to platelets was diminished by alpha (IIb)beta (3) antagonists or by a genetic defect in this integrin. Integrin alpha (IIb)beta (3) undergoes a conformational change upon platelet activation, and bacteria bound more efficiently to activated rather than resting platelets. Nevertheless, B. hermsii bound at detectable levels to preparations of resting platelets. The bacterium did not recognize a point mutant of alpha (IIb)beta (3) that cannot acquire an active conformation. Rather, B. hermsii was capable of triggering platelet and integrin alpha (IIb)beta (3) activation, as indicated by the expression of the platelet activation marker P-selectin and integrin alpha (IIb)beta (3) in its active conformation. The degree of platelet activation varied depending upon bacterial strain and growth conditions. Prostacyclin I-2, an inhibitor of platelet activation, diminished bacterial attachment, indicating that activation enhanced bacterial binding. Thus, B. hermsii signals the host cell to activate a critical receptor for the bacterium, thereby promoting high-level bacterial attachment.