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Virulence and thrombocyte affectation of two Aspergillus terreus isolates differing in amphotericin B susceptibility
Cornelia Speth1, Gerhard Blum, Magdalena Hagleitner
1Division of Hygiene and Medical Microbiology, Innsbruck Medical University, Fritz-Pregl-Straße 3, 6020, Innsbruck, Austria.
Abstract:
Aspergillus terreus-induced invasive infections exhibit high lethality, partly due to the intrinsic resistance for amphotericin B (AmB). We compared the virulence and pathogenesis of an AmB-resistant isolate of A. terreus (ATR) with that of a rare variant showing enhanced sensitivity for AMB (ATS). The modifications that result in enhanced AmB sensitivity of isolates are not associated with reduced virulence in vivo; instead, the ATS-infected mice died even faster than the ATR-infected animals. Since A. terreus enters the blood stream in most patients and frequently induces thrombosis, we studied a putative correlation between virulence of the two A. terreus isolates and their effect on thrombocytes. Those mice infected with the more virulent ATS isolate had lower thrombocyte numbers and more phosphatidylserine exposure on platelets than ATR-infected mice. In vitro experiments confirmed that ATS and ATR differ in their effect on thrombocytes. Conidia, aleurioconidia and hyphae of ATS were more potent than ATR to trigger thrombocyte stimulation, and thrombocytes adhered better to ATS than to ATR fungal structures. Furthermore, ATS secreted more soluble factors that triggered platelet stimulation than ATR. Thus, it might be suggested that the capacity of a fungal isolate to modulate thrombocyte parameters contributes to its virulence in vivo.
Insights
Invasive Aspergillus terreus infections are deadly, even when the fungus is sensitive to amphotericin B (AmB). A highly sensitive strain showed increased virulence by more potently affecting blood platelets and thrombosis.
Area of Science:
- Mycology
- Infectious Diseases
- Hematology
Background:
- Invasive Aspergillus terreus infections are a significant cause of mortality.
- Amphotericin B (AmB) resistance in A. terreus contributes to treatment challenges.
- The pathogenesis of A. terreus, particularly its interaction with host factors like platelets, requires further investigation.
Purpose of the Study:
- To compare the virulence and pathogenesis of an AmB-resistant A. terreus (ATR) isolate with an AmB-sensitive A. terreus (ATS) isolate.
- To investigate the correlation between the virulence of A. terreus isolates and their impact on thrombocytes (platelets).
- To elucidate the role of fungal-platelet interactions in A. terreus-induced invasive infections.
Main Methods:
- Comparative analysis of in vivo virulence between ATR and ATS isolates in a mouse model.
- Assessment of thrombocyte counts and phosphatidylserine exposure on platelets in infected mice.
- In vitro experiments evaluating fungal conidia, aleurioconidia, hyphae, and secreted factors' effects on thrombocyte stimulation and adhesion.
Main Results:
- The AmB-sensitive ATS isolate exhibited greater virulence in vivo, leading to faster mortality compared to the ATR isolate.
- ATS infection resulted in significantly lower thrombocyte counts and increased phosphatidylserine exposure on platelets.
- In vitro studies demonstrated that ATS more potently stimulated thrombocytes and enhanced platelet adhesion to fungal structures than ATR.
Conclusions:
- Enhanced sensitivity to amphotericin B does not necessarily reduce the virulence of Aspergillus terreus.
- Aspergillus terreus virulence is associated with its capacity to modulate thrombocyte parameters, including stimulation and adhesion.
- Fungal-induced thrombocyte activation and subsequent thrombosis may be a critical factor in the pathogenesis of invasive A. terreus infections.
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