title: Virulence and thrombocyte affectation of two Aspergillus terreus isolates differing in amphotericin B susceptibility.
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.
authors.affiliation: Division of Hygiene and Medical Microbiology, Innsbruck Medical University, Fritz-Pregl-Straße 3, 6020, Innsbruck, Austria.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Speth
authors.forename: Gerhard
authors.initials: G
authors.lastname: Blum
authors.forename: Magdalena
authors.initials: M
authors.lastname: Hagleitner
authors.forename: Caroline
authors.initials: C
authors.lastname: Hörtnagl
authors.forename: Kristian
authors.initials: K
authors.lastname: Pfaller
authors.forename: Beate
authors.initials: B
authors.lastname: Posch
authors.forename: Helmut Werner
authors.initials: HW
authors.lastname: Ott
authors.forename: Reinhard
authors.initials: R
authors.lastname: Würzner
authors.forename: Cornelia
authors.initials: C
authors.lastname: Lass-Flörl
authors.forename: Günter
authors.initials: G
authors.lastname: Rambach
mesh_terms: D000666:Amphotericin B / Q000494:pharmacology*; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D001228:Aspergillosis / Q000382:microbiology* / Q000473:pathology*; D001230:Aspergillus / Q000187:drug effects / Q000472:pathogenicity*; D001792:Blood Platelets / Q000382:microbiology* / Q000502:physiology; D002448:Cell Adhesion; D004195:Disease Models, Animal; D025141:Drug Resistance, Fungal; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D016019:Survival Analysis; D013921:Thrombocytopenia; D014774:Virulence
chemical_list: D000935:Antifungal Agents; D000666:Amphotericin B