title: Aspergillus tanneri sp. nov., a new pathogen that causes invasive disease refractory to antifungal therapy.
abstract: The most common cause of invasive aspergillosis (IA) in patients with chronic granulomatous disease (CGD) is Aspergillus fumigatus followed by A. nidulans; other aspergilli rarely cause the disease. Here we review two clinical cases of fatal IA in CGD patients and describe a new etiologic agent of IA refractory to antifungal therapy. Unlike typical IA caused by A. fumigatus, the disease caused by the new species was chronic and spread from the lung to multiple adjacent organs. Mycological characteristics and the phylogenetic relationship with other aspergilli based on the sequence analysis of Mcm7, RPB2, and Tsr1 indicated that the new species, which we named as A. tanneri, belongs to Aspergillus section Circumdati. The species has a higher amphotericin B, voriconazole, and itraconazole MIC and causes more chronic infection in CGD mice than A. fumigatus. This is the first report documenting IA in CGD patients caused by a species belonging to the Aspergillus section Circumdati that is inherently resistant to azoles and amphotericin B. Unlike the results seen with many members of Aspergillus section Circumdati, ochratoxin was not detected in filtrates of cultures grown in various media. Our phenotypic and genetic characterization of the new species and the case reports will assist future diagnosis of infection caused by A. tanneri and lead to more appropriate patient management.
authors.affiliation: Laboratory of Clinical Infectious Diseases, NIAID, NIH, Bethesda, MD, USA.
authors.forename: Janyce A
authors.initials: JA
authors.lastname: Sugui
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Peterson
authors.forename: Lily P
authors.initials: LP
authors.lastname: Clark
authors.forename: Glenn
authors.initials: G
authors.lastname: Nardone
authors.forename: Les
authors.initials: L
authors.lastname: Folio
authors.forename: Gregory
authors.initials: G
authors.lastname: Riedlinger
authors.forename: Christa S
authors.initials: CS
authors.lastname: Zerbe
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Shea
authors.forename: Christina M
authors.initials: CM
authors.lastname: Henderson
authors.forename: Adrian M
authors.initials: AM
authors.lastname: Zelazny
authors.forename: Steven M
authors.initials: SM
authors.lastname: Holland
authors.forename: Kyung J
authors.initials: KJ
authors.lastname: Kwon-Chung
mesh_terms: D000293:Adolescent; D000666:Amphotericin B / Q000494:pharmacology; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001228:Aspergillosis / Q000175:diagnosis / Q000188:drug therapy / Q000382:microbiology* / Q000473:pathology; D001230:Aspergillus / Q000145:classification* / Q000187:drug effects / Q000235:genetics* / Q000302:isolation & purification; D016000:Cluster Analysis; D004271:DNA, Fungal / Q000737:chemistry / Q000235:genetics; D025141:Drug Resistance, Fungal; D005656:Fungal Proteins / Q000235:genetics; D006105:Granulomatous Disease, Chronic / Q000175:diagnosis / Q000188:drug therapy / Q000382:microbiology / Q000473:pathology; D006801:Humans; D017964:Itraconazole / Q000494:pharmacology; D008168:Lung / Q000000981:diagnostic imaging / Q000473:pathology; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D008853:Microscopy; D008969:Molecular Sequence Data; D010802:Phylogeny; D011743:Pyrimidines / Q000494:pharmacology; D017422:Sequence Analysis, DNA; D014057:Tomography, X-Ray Computed; D017211:Treatment Failure; D014230:Triazoles / Q000494:pharmacology; D065819:Voriconazole; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D004271:DNA, Fungal; D005656:Fungal Proteins; D011743:Pyrimidines; D014230:Triazoles; D017964:Itraconazole; D000666:Amphotericin B; D065819:Voriconazole