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Infection and Immunity, August 2000, p. 4699-4705, Vol. 68, No. 8
The Anti-Infective Research Laboratory,
Detroit Receiving Hospital/University Health Center and College of
Pharmacy,1 and Department of Internal
Medicine, School of Medicine, Wayne State
University,3 Detroit, Michigan 48201;
University of New Mexico-College of Pharmacy, Albuquerque, New
Mexico 871312; Department of Medicine,
Division of Infectious Diseases, St. John's Cardiovascular Research
Center, LAC-Harbor UCLA Medical Center Research and Education
Institute, Torrance, California 905024; and
School of Medicine, University of California, Los Angeles,
California 900245
Received 16 March 2000/Returned for modification 27 April
2000/Accepted 15 May 2000
Several lines of evidence indicate that platelets protect against
endovascular infections such as infective endocarditis (IE). It is
highly likely that a principal mechanism of this platelet host defense
role is the release of platelet microbicidal proteins (PMPs) in
response to agonists generated at sites of endovascular infection. We
studied the ability of platelets to limit the colonization and
proliferation of Staphylococcus aureus in an in vitro model of IE. Three isogenic S. aureus strains, differing in their
in vitro susceptibility to thrombin-induced platelet microbicidal protein-1 (tPMP), were used: ISP479C (parental strain; highly susceptible to tPMP [tPMPs]); ISP479R (transposon mutant
derived from ISP479; tPMP resistant [tPMPr]); or 757-5 (tPMPr transductant of the ISP479R genotype in the ISP479
parental background). Time-kill assays and in vitro IE models were used
to examine the temporal relationship between thrombin-induced platelet
activation and S. aureus killing. In time-kill studies,
early platelet activation (30 min prior to bacterial exposure)
correlated with a significant bactericidal effect against
tPMPs ISP479C (r2 > 0.90, P < 0.02) but not against tPMPr strains,
ISP479R or 757-5. In the IE model, thrombin activation significantly
inhibited proliferation of ISP479C within simulated vegetations
compared to strains ISP479R or 757-5 (P < 0.05). The latter differences were observed despite there being no detectable differences among the three S. aureus strains in initial
colonization of simulated vegetations. Collectively, these data
indicate that platelets limit intravegetation proliferation of
tPMPs but not tPMPr S. aureus.
These findings underscore the likelihood that platelets play an
important antimicrobial host defense role in preventing and/or limiting
endovascular infections due to tPMPs pathogens.
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Influence of Platelets and Platelet Microbicidal
Protein Susceptibility on the Fate of Staphylococcus aureus
in an In Vitro Model of Infective Endocarditis
*
Corresponding author. Mailing address: University of
New Mexico/College of Pharmacy, 2502 Marble NE, Albuquerque, NM 87131. Phone: (505) 272-0581. Fax: (505) 272-6749. E-mail:
rmercier{at}unm.edu.
Infection and Immunity, August 2000, p. 4699-4705, Vol. 68, No. 8
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
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