Aspergillus fumigatus
SusceptibilityThe Siderophore Transporter Sit1 Determines Susceptibility to the Antifungal VL-2397VL-2397 (previously termed ASP2397) is an antifungal, aluminum-chelating cyclic hexapeptide with a structure analogous to that of ferrichrome-type siderophores, whereby replacement of aluminum by iron was shown to decrease the antifungal activity of this compound. Here, we found that inactivation of an importer for ferrichrome-type siderophores, termed Sit1, renders ...
Experimental TherapeuticsExtended-Interval Dosing of Rezafungin against Azole-Resistant Aspergillus fumigatusWe evaluated extended-interval dosing of the investigational echinocandin rezafungin (1, 4, and 16 mg/kg on days 1, 4, and 7 postinoculation) for the treatment of disseminated invasive aspergillosis caused by azole-resistant Aspergillus fumigatus. Survival was significantly improved in mice treated with each dose of rezafungin and supratherapeutic posaconazole (20 mg/...
Epidemiology and SurveillanceElevated Prevalence of Azole-Resistant Aspergillus fumigatus in Urban versus Rural Environments in the United KingdomAzole resistance in the opportunistic pathogen Aspergillus fumigatus is increasing, dominated primarily by the following two environmentally associated resistance alleles: TR34/L98H and TR46/Y121F/T289A. By sampling soils across the South of England, we assess the prevalence of azole-resistant...
PharmacologyEfficacy of Olorofim (F901318) against Aspergillus fumigatus, A. nidulans, and A. tanneri in Murine Models of Profound Neutropenia and Chronic Granulomatous DiseaseThe emergence of azole resistance in Aspergillus fumigatus as well as an increasing frequency of multiresistant cryptic Aspergillus spp. necessitates exploration of new classes of antifungals.
Experimental TherapeuticsIn Vitro and In Vivo Exposure-Effect Relationship of Liposomal Amphotericin B against Aspergillus fumigatusIn vitro pharmacokinetic/pharmacodynamic data of liposomal amphotericin B (L-AMB) were compared with animal data from neutropenic and nonneutropenic models of azole-susceptible and azole-resistant invasive aspergillosis. L-AMB was equally effective.
Experimental TherapeuticsStructure, Mechanism, and Inhibition of Aspergillus fumigatus Thioredoxin ReductaseAspergillus fumigatus infections are associated with high mortality rates and high treatment costs. Limited available antifungals and increasing antifungal resistance highlight an urgent need for new antifungals.
Experimental TherapeuticsImpact of Antifungal Compounds on Viability and Anti-Aspergillus Activity of Human Natural Killer CellsDespite the availability of new antifungal compounds, invasive aspergillosis carries high morbidity and mortality in hematopoietic stem cell transplant recipients. In vitro studies and animal models suggest that the adoptive transfer of natural killer (NK) cells might be a promising immunotherapeutic option in this setting.
Clinical TherapeuticsPreexposure to Isavuconazole Increases the Virulence of Mucorales but Not Aspergillus fumigatus in a Drosophila melanogaster Infection ModelBreakthrough mucormycosis in patients receiving isavuconazole prophylaxis or therapy has been reported. We compared the impact of isavuconazole and voriconazole exposure on the virulence of clinical isolates of Aspergillus fumigatus and different Mucorales species in a Drosophila melanogaster...
Mechanisms of Action: Physiological EffectsInducible Cell Fusion Permits Use of Competitive Fitness Profiling in the Human Pathogenic Fungus Aspergillus fumigatus...Antifungal agents directed against novel therapeutic targets are required for treating invasive, chronic, and allergic Aspergillus infections. Competitive fitness profiling technologies have been used in a number of bacterial and yeast systems to identify druggable targets; however, the development of similar systems in filamentous fungi is complicated by the fact that they undergo cell fusion and heterokaryosis.
Mechanisms of ResistanceFirst Clinical Isolation of an Azole-Resistant Aspergillus fumigatus Isolate Harboring a TR46 Y121F T289A Mutation in South AmericaOne of the most recently described Aspergillus fumigatus CYP51A-mediated azole resistance mechanisms is TR46 Y121F T289A. Clinical A. fumigatus strains harboring these substitutions have been reported worldwide, with the exception of South America.