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Med Microbiol Immunol (2013) 202:379389 DOI 10.1007/s00430-013-0300-7
ORIGINAL INVESTIGATION
Virulence and thrombocyte affectation of two Aspergillus terreus isolates differing in amphotericin B susceptibility
Cornelia Speth Gerhard Blum Magdalena Hagleitner Caroline Hrtnagl
Kristian Pfaller Beate Posch Helmut Werner Ott Reinhard Wrzner
Cornelia Lass-Flrl Gnter Rambach
Received: 14 February 2013 / Accepted: 17 May 2013 / Published online: 31 May 2013 Springer-Verlag Berlin Heidelberg 2013
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 modications 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. SinceA. 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 conrmed 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.
Keywords Aspergillus Fungal infection Virulence
Pathogenesis Thrombocytes
Introduction
Invasive fungal infections (IFI) represent a signicant determinant of morbidity and mortality in patients with compromised immunity due to cancer chemotherapy, hematopoietic stem-cell transplantation and solid organ transplantation, but also in non-traditional hosts such as patients with chronic obstructive pulmonary disease (COPD) [15]. Despite the recent advances in antifungal therapy, these infections remain difcult to be managed because of risk for dissemination and a mostly late diagnosis [6]. Aspergillus (A.) spp., a widespread soil saprophyte, is one predominant species to induce IFI withA. fumigatus and A. terreus being the most pathogenic species [7]. At some institutions (e.g. the Medical University Hospital of Innsbruck, Austria,...