Faculty Collaboration Database

Platelet activation by a relapsing fever spirochaete results in enhanced bacterium-platelet interaction via integrin alphaIIbbeta3 activation. Mol Microbiol 2001 Jan;39(2):330-40

Date

01/03/2001

Pubmed ID

11136454

DOI

10.1046/j.1365-2958.2001.02201.x

Scopus ID

2-s2.0-0035151055 (requires institutional sign-in at Scopus site)   42 Citations

Abstract

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.

Author List

Alugupalli KR, Michelson AD, Barnard MR, Robbins D, Coburn J, Baker EK, Ginsberg MH, Schwan TG, Leong JM

Author

Jenifer Coburn PhD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Blood Platelets
Borrelia
CHO Cells
Cricetinae
Culture Media
Humans
Mice
Mice, Inbred C57BL
Mutation
Platelet Activation
Platelet Glycoprotein GPIIb-IIIa Complex
Protein Conformation
Relapsing Fever
Transfection