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Disseminated intravascular coagulation associated with Staphylococcus aureus septicemia is mediated by
C M Kessler1, E Nussbaum, C U Tuazon
1Division of Hematology-Oncology, George Washington University Medical Center, Washington, DC.
Abstract:
Disseminated intravascular coagulation (DIC) may complicate severe septicemia caused by Staphylococcus aureus. S. aureus can induce spontaneous platelet aggregation in vitro, the rapidity and degree of which correlates with the severity of DIC in patients with sepsis. Purified peptidoglycan from DIC isolates aggregated human platelets in the presence of staphylococcal protein A with significantly shorter aggregation times than did peptidoglycan from non-DIC isolates. Purified teichoic acid from DIC and non-DIC isolates failed to aggregate platelets in vitro, or in vivo in guinea pigs but inhibited the peptidoglycan-induced aggregation in a dose-response manner. These studies suggest that peptidoglycan may mediate S. aureus-induced spontaneous platelet aggregation in vitro and DIC in vivo. The variability among strains of S. aureus to induce DIC and platelet aggregation may depend on the unique composition of their peptidoglycan and perhaps also the extent of exposure or availability of cell wall teichoic acid.
Insights
Staphylococcus aureus peptidoglycan, especially from sepsis isolates, triggers platelet aggregation and may cause disseminated intravascular coagulation (DIC). Teichoic acid inhibits this effect, suggesting cell wall composition influences DIC severity.
Area of Science:
- Microbiology
- Hematology
- Immunology
Background:
- Severe septicemia caused by Staphylococcus aureus can lead to disseminated intravascular coagulation (DIC).
- Staphylococcus aureus exhibits the ability to induce spontaneous platelet aggregation in vitro.
- The extent and speed of platelet aggregation correlate with DIC severity in sepsis patients.
Purpose of the Study:
- To investigate the role of Staphylococcus aureus cell wall components, specifically peptidoglycan and teichoic acid, in inducing platelet aggregation.
- To determine if bacterial isolates from DIC patients exhibit different platelet aggregation-inducing properties compared to non-DIC isolates.
- To elucidate the mechanisms by which S. aureus contributes to DIC pathogenesis.
Main Methods:
- Purification of peptidoglycan and teichoic acid from Staphylococcus aureus isolates associated with DIC and non-DIC sepsis.
- In vitro assessment of human platelet aggregation induced by purified bacterial components, with and without staphylococcal protein A.
- In vivo studies in guinea pigs to evaluate the effects of teichoic acid on platelet aggregation.
- Dose-response inhibition assays using teichoic acid on peptidoglycan-induced platelet aggregation.
Main Results:
- Purified peptidoglycan from DIC isolates induced human platelet aggregation more rapidly than peptidoglycan from non-DIC isolates, in the presence of staphylococcal protein A.
- Purified teichoic acid did not induce platelet aggregation in vitro or in vivo.
- Teichoic acid demonstrated a dose-dependent inhibitory effect on peptidoglycan-induced platelet aggregation.
Conclusions:
- Staphylococcus aureus peptidoglycan is implicated as a mediator of spontaneous platelet aggregation and potentially DIC in vivo.
- The composition of S. aureus peptidoglycan may explain strain variability in inducing DIC and platelet aggregation.
- Teichoic acid may play a regulatory role by inhibiting peptidoglycan-induced platelet aggregation, influencing DIC outcomes.