Purpose: Aspergillus fumigatus (Af) is a major pathogenic fungus of invasive aspergillosis. Recently reports on aspergillosis by A. lentulus (Al) and A. udagawae (Au), the relative fungi of Af, are on the increase. Although these species are similar to Af in morphology and often misidentified as the fungus, some studies reported that Al and Au have low susceptibility to several antifungal agents. However, the detailed knowledge on these species is still limited. In this study, we investigated their susceptibility to antifungal agents and the production of mycotoxins, particularly gliotoxin. Methods: Twenty one Af, eight Al and eight Au strains, isolated from clinical and environmental samples and stored in our culture collection, were used. Antifungal susceptibility testes were performed based on the clinical and laboratory standards institute (CLSI) M38-A2 method. For mycotoxins analysis, conidia were soaked in methanol for overnight, then the extracts were analyzed by LC/TOF-MS and LC/MS/MS. Culture filtrates of the fungi were extracted with chloroform, and were also analyzed. Results: The MICs of Af, Al and Au were similar in micafungin, fluconazole and flucytosine. Al and Au showed slightly low susceptibility to amphotericin B. In contrast, MICs of voriconazole and itraconazole were higher in Al and Au than Af (Al: 2 to 8 μg/ml, Au: 0.5 to 8 μg/ml, Af: 0.12 to 0.5 μg/ml in voriconazole; Al: 0.25 to 1 μg/ml, Au: 0.25 to 8 μg/ml, Af: 0.12 to 0.5 μg/ml in itraconazole). Strains of Au with high voriconazole MIC also showed high MIC to itraconazole. The concentration of gliotoxin in extracts of culture filtrates was higher than in extracts of conidia. Although some isolates of Al and Au also produced gliotoxin, the incidence of the production in culture filtrate was highest among Af (90.5% in Af; 12.5% in Al; 50.0% in Au). There was no relationship between the concentration of gliotoxin produced and the MIC profile in any of the three species. Again no difference was detected in gliotoxin production between clinical and environmental isolates in any of the species. Conclusions: Al and Au have low susceptibility to azole antifungal drugs (voriconazole and itraconazole), which indicates that precise identification is required for optimal antifungal treatment. These fungi are known to cause serious disseminated infections, and low gliotoxin production by Al and Au suggests that these fungi may be using other virulence factors for infection.
Full conference title:
4th Advances Against Aspergillosis
- AAA 4th (2010)