Platelet activation by a relapsing fever spirochaete results in enhanced bacterium-platelet interaction via integrin alphaIIbbeta3 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 alphaIIbbeta3: the bacterium bound to purified integrin alphaIIbbeta3, and bacterial binding to platelets was diminished by alphaIIbbeta3 antagonists or by a genetic defect in this integrin. Integrin alphaIIbbeta3 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 alphaIIbbeta3 that cannot acquire an active conformation. Rather, B. hermsii was capable of triggering platelet and integrin alphaIIbbeta3 activation, as indicated by the expression of the platelet activation marker P-selectin and integrin alphaIIbbeta3 in its active conformation. The degree of platelet activation varied depending upon bacterial strain and growth conditions. Prostacyclin I2, 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.
Alugupalli
K R
KR
Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA.
Michelson
A D
AD
Barnard
M R
MR
Robbins
D
D
Coburn
J
J
Baker
E K
EK
Ginsberg
M H
MH
Schwan
T G
TG
Leong
J M
JM
D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D001898:Borrelia / Q000378:metabolism* / Q000472:pathogenicity*; D016466:CHO Cells; D006224:Cricetinae; D003470:Culture Media; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D015539:Platelet Activation / Q000502:physiology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011487:Protein Conformation; D012061:Relapsing Fever / Q000382:microbiology*; D014162:Transfection
D003470:Culture Media; D019039:Platelet Glycoprotein GPIIb-IIIa Complex