Molecular identification and antifungal susceptibility of clinically relevant and cryptic species of Aspergillus sections Flavi and Nigri

Abstract

Introduction. Aspergillus sections Flavi and Nigri comprise clinically relevant and cryptic species that differ significantly in drug susceptibility, meaning that effective treatment depends on correct species identification. Hypothesis/Gap Statement. There are no comprehensive data for molecular identification and antifungal susceptibility testing (AFST) of clinically relevant and cryptic species of Aspergillus sections Flavi and Nigri as the main agents of invasive and non-invasive aspergillosis in Iran. We aimed to perform molecular identification and AFST of 213 clinical Aspergillus isolates belonging to sections Flavi and Nigri. Molecular identification of isolates was performed using sequencing of the β-tubulin gene and in vitro AFST was conducted according to the Clinical and Laboratory Standards Institute (CLSI) M38-A3 guidelines. Results. The most common isolates in sections Flavi and Nigri were Aspergillus flavus (110/113, 97.3 %) and Aspergillus tubingensis (49/100, 49.0 %), respectively. A total of 62/213 (29.1 %) isolates belonging to cryptic species were identified; among them, A. tubingensis was the most prevalent (49/62, 79.0%). Aspergillus flavus and A. niger isolates that responded to the minimum inhibitory concentrations (MICs) of itraconazole above the epidemiological cutoff values were the most frequently detected: 8/110 (7.3 %) and 3/41 (7.3 %), respectively. In section Flavi, Aspergillus alliaceus responded to amphotericin B at a high MIC (>16 µg mL−1) and in section Nigri, one of the three Aspergillus luchuensis/awamori isolates responded to itraconazole at an MIC >16 µg ml−1. Interestingly, for all Aspergillus welwitschiae isolates, the MIC50 and MIC90 of itraconazole were both 16 µg ml−1. Conclusion. A considerable presence of A. flavus and A. niger isolates showing non-wild-type responses to azoles in clinical cases of aspergillosis indicates the importance of classifying clinical Aspergillus isolates at the species level and performing antifungal susceptibility testing on the isolates, which would ensure appropriate treatment.

Genomic and Phenotypic Trait Variation of the Opportunistic Human Pathogen Aspergillus flavus and Its Close Relatives

“…Resistance to antifungal drugs was also similar between strains of the same species and within previously reported ranges for A. flavus ( 104 ). Our A. flavus and A. parasiticus strains were more susceptible to amphotericin B than clinical strains of the same species from Brazil ( 105 ), and strains from all four species had similar susceptibility to voriconazole as clinical strains from Brazil ( 106 , 107 ).…”

Genomic and phenotypic trait variation of the opportunistic human pathogen Aspergillus flavus and its non-pathogenic close relatives

“…Resistance to antifungal drugs was also similar between strains of the same species and within previously reported ranges for A. flavus (67). Our A. flavus and A. parasiticus strains were more susceptible to amphotericin B than clinical strains of the same species from Brazil (68), and strains from all four species had similar susceptibility to voriconazole as clinical strains from Brazil (69,70).…”

Multicenter Italian Study on “In Vitro Activities” of Isavuconazole, Voriconazole, Amphotericin B, and Caspofungin for Aspergillus Species: Comparison between SensititreTM YeastOneTM and MIC Test Strip

“…MIC test strip overestimation was previously described by other authors. 22 These phenotypes could be correlated to cryptic species as A. lentulus, morphologically indistinguishable from A. fumigatus sensu stricto, or other cryptic species in flavi and nigri sections, revealing the emerging importance of molecular species identification, as reported by Nargesi et al 23,24…”