Secondary metabolite profiles and antifungal drug susceptibility of Aspergillus fumigatus and closely related species, Aspergillus lentulus, Aspergillus udagawae, and Aspergillus viridinutans.
The incidence of Aspergillus infection has been increasing in the past few years. Also, new Aspergillus fumigatus-related species, namely Aspergillus lentulus, Aspergillus udagawae, and Aspergillus viridinutans, were shown to infect humans. These fungi exhibit marked morphological similarities to A. fumigatus, albeit with different clinical courses and antifungal drug susceptibilities. The present study used liquid chromatography/time-of-flight mass spectrometry to identify the secondary metabolites secreted as virulence factors by these Aspergillus species and compared their antifungal susceptibility. The metabolite profiles varied widely among A. fumigatus, A. lentulus, A. udagawae, and A. viridinutans, producing 27, 13, 8, and 11 substances, respectively. Among the mycotoxins, fumifungin, fumiquinazoline A/B and D, fumitremorgin B, gliotoxin, sphingofungins, pseurotins, and verruculogen were only found in A. fumigatus, whereas auranthine was only found in A. lentulus. The amount of gliotoxin, one of the most abundant mycotoxins in A. fumigatus, was negligible in these related species. In addition, they had decreased susceptibility to antifungal agents such as itraconazole and voriconazole, even though metabolites that were shared in the isolates showing higher minimum inhibitory concentrations than epidemiological cutoff values were not detected. These strikingly different secondary metabolite profiles may lead to the development of more discriminative identification protocols for such closely related Aspergillus species as well as improved treatment outcomes.
Division of Fungal Infection, Medical Mycology Research Center, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8673, Japan; Department of Respiratory Medicine, The University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan; Division of Clinical Research, Medical Mycology Research Center, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8677, Japan. Electronic address: tamiya-nii@umin.ac.jp.
Hiroyuki
H
Tamiya
Division of Fungal Infection, Medical Mycology Research Center, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8673, Japan.
Eri
E
Ochiai
Division of Bio-resources, Medical Mycology Research Center, Chiba University, Chiba, Japan.
Kazuyo
K
Kikuchi
Division of Fungal Infection, Medical Mycology Research Center, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8673, Japan.
Maki
M
Yahiro
Division of Fungal Infection, Medical Mycology Research Center, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8673, Japan.
Takahito
T
Toyotome
Division of Fungal Infection, Medical Mycology Research Center, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8673, Japan; Division of Clinical Research, Medical Mycology Research Center, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8677, Japan; Division of Control and Treatment of Infectious Diseases, Chiba University Hospital, 1-8-1 Inohana, Chuo-ku, Chiba 260-8677, Japan.
Akira
A
Watanabe
Division of Bio-resources, Medical Mycology Research Center, Chiba University, Chiba, Japan.
Takashi
T
Yaguchi
Division of Fungal Infection, Medical Mycology Research Center, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8673, Japan; Division of Clinical Research, Medical Mycology Research Center, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8677, Japan; Division of Control and Treatment of Infectious Diseases, Chiba University Hospital, 1-8-1 Inohana, Chuo-ku, Chiba 260-8677, Japan.
Katsuhiko
K
Kamei
D000935:Antifungal Agents / Q000494:pharmacology; D001228:Aspergillosis / Q000382:microbiology*; D001230:Aspergillus / Q000187:drug effects* / Q000378:metabolism*; D001232:Aspergillus fumigatus / Q000187:drug effects / Q000378:metabolism; D005912:Gliotoxin / Q000032:analysis* / Q000096:biosynthesis; D006801:Humans; D017964:Itraconazole / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D037521:Virulence Factors / Q000032:analysis* / Q000096:biosynthesis; D065819:Voriconazole / Q000494:pharmacology
D000935:Antifungal Agents; D037521:Virulence Factors; D017964:Itraconazole; D005912:Gliotoxin; D065819:Voriconazole
Aspergillus fumigatus; Aspergillus lentulus; Aspergillus udagawae; Aspergillus viridinutans; Liquid chromatography/time-of-flight mass spectrometry; Secondary metabolites