Draft Genome Sequences of Four
            <i>Aspergillus</i>
            Section
            <i>Fumigati</i>
            Clinical Strains

Santos, Renato Augusto Corrêa dos; Rivero-Menéndez, Olga; Steenwyk, Jacob L.; Mead, Matthew E.; Goldman, Gustavo H.; Alastruey‐Izquierdo, Ana; Rokas, Antonis

doi:10.1128/mra.00856-20

Cited by 4 publications

(10 citation statements)

References 22 publications

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“…The best-fitting substitution model—TIM3 with empirical base frequencies, allowing for a proportion of invariable sites, and a discrete Gamma model ( 95 , 96 ) with four rate categories (TIM3+F+I+G4)—was determined using the Bayesian information criterion. In the second analysis, the same process was used to conduct molecular phylogenetic analysis using calmodulin nucleotide sequences from Aspergillus section Fumigati species and Aspergillus clavatus , an outgroup taxon, using sequences from NCBI that were made available elsewhere ( 97 ). For calmodulin sequences, the best-fitting substitution model was TNe ( 98 ) with a discrete Gamma model with four rate categories (TNe+G4).…”

Section: Methodsmentioning

confidence: 99%

Genomic and Phenotypic Analysis of COVID-19-Associated Pulmonary Aspergillosis Isolates of Aspergillus fumigatus

et al. 2021

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Section: Methodsmentioning

confidence: 99%

Genomic and Phenotypic Analysis of COVID-19-Associated Pulmonary Aspergillosis Isolates of Aspergillus fumigatus

et al. 2021

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“…VCZ resistance is not restricted to A. fumigatus sensu stricto and occurs in other species of the section Fumigati. The Fumigati contains closely related species that are morphologically indistinguishable from A. fumigatus [82]. Among sibling species pathogenic in humans are A. lentulus and A. felis [83].…”

Section: Aspergillus Speciesmentioning

confidence: 99%

Sterol 14α-Demethylase Ligand-Binding Pocket-Mediated Acquired and Intrinsic Azole Resistance in Fungal Pathogens

Rosam

Monk

Lackner

2020

JoF

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The fungal cytochrome P450 enzyme sterol 14α-demethylase (SDM) is a key enzyme in the ergosterol biosynthesis pathway. The binding of azoles to the active site of SDM results in a depletion of ergosterol, the accumulation of toxic intermediates and growth inhibition. The prevalence of azole-resistant strains and fungi is increasing in both agriculture and medicine. This can lead to major yield loss during food production and therapeutic failure in medical settings. Diverse mechanisms are responsible for azole resistance. They include amino acid (AA) substitutions in SDM and overexpression of SDM and/or efflux pumps. This review considers AA affecting the ligand-binding pocket of SDMs with a primary focus on substitutions that affect interactions between the active site and the substrate and inhibitory ligands. Some of these interactions are particularly important for the binding of short-tailed azoles (e.g., voriconazole). We highlight the occurrence throughout the fungal kingdom of some key AA substitutions. Elucidation of the role of these AAs and their substitutions may assist drug design in overcoming some common forms of innate and acquired azole resistance.

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“…Antifungal susceptibility testing (AST) was conducted for four Aspergillus isolates and these results were merged with those from a previous publication (Dos Santos et al, 2020a ). We used the EUCAST (European Committee for Antimicrobial Susceptibility Testing) reference microdilution method version 9.3.2 ( https://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/AFST/Files/EUCAST_E_Def_9.3.2_Mould_testing_definitive_revised_2020.pdf ) (Arendrup et al, 2015 ), in which isolates are grown on plates with increasing drug concentrations and the first concentration in which growth is inhibited (MIC) is recorded.…”

Section: Methodsmentioning

confidence: 99%

“…We used the EUCAST (European Committee for Antimicrobial Susceptibility Testing) reference microdilution method version 9.3.2 ( https://www.eucast.org/fileadmin/src/media/PDFs/EUCAST_files/AFST/Files/EUCAST_E_Def_9.3.2_Mould_testing_definitive_revised_2020.pdf ) (Arendrup et al, 2015 ), in which isolates are grown on plates with increasing drug concentrations and the first concentration in which growth is inhibited (MIC) is recorded. For the four isolates of A. hiratsukae and A. felis recently sequenced by our group (Dos Santos et al, 2020a ), we tested their susceptibility to four antifungal drug classes as previously described (Dos Santos et al, 2020b ).…”

Section: Methodsmentioning

confidence: 99%

Examining Signatures of Natural Selection in Antifungal Resistance Genes Across Aspergillus Fungi

Santos

Mead

Steenwyk

et al. 2021

Front. Fungal Biol.

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Certain Aspergillus fungi cause aspergillosis, a set of diseases that typically affect immunocompromised individuals. Most cases of aspergillosis are caused by Aspergillus fumigatus, which infects millions of people annually. Some closely related so-called cryptic species, such as Aspergillus lentulus, can also cause aspergillosis, albeit at lower frequencies, and they are also clinically relevant. Few antifungal drugs are currently available for treating aspergillosis and there is increasing worldwide concern about the presence of antifungal drug resistance in Aspergillus species. Furthermore, isolates from both A. fumigatus and other Aspergillus pathogens exhibit substantial heterogeneity in their antifungal drug resistance profiles. To gain insights into the evolution of antifungal drug resistance genes in Aspergillus, we investigated signatures of positive selection in 41 genes known to be involved in drug resistance across 42 susceptible and resistant isolates from 12 Aspergillus section Fumigati species. Using codon-based site models of sequence evolution, we identified ten genes that contain 43 sites with signatures of ancient positive selection across our set of species. None of the sites that have experienced positive selection overlap with sites previously reported to be involved in drug resistance. These results identify sites that likely experienced ancient positive selection in Aspergillus genes involved in resistance to antifungal drugs and suggest that historical selective pressures on these genes likely differ from any current selective pressures imposed by antifungal drugs.

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Draft Genome Sequences of Four Aspergillus Section Fumigati Clinical Strains

Abstract: Aspergillus fungi in section Fumigati include important human pathogens. Here, we sequenced the genomes of two strains of Aspergillus hiratsukae and two strains of Aspergillus felis. The average genome sizes are 29.5 Mb for A. hiratsukae and 31.8 Mb for A. felis.

Cited by 4 publications

References 22 publications

Genomic and Phenotypic Analysis of COVID-19-Associated Pulmonary Aspergillosis Isolates of Aspergillus fumigatus

Genomic and Phenotypic Analysis of COVID-19-Associated Pulmonary Aspergillosis Isolates of Aspergillus fumigatus

Sterol 14α-Demethylase Ligand-Binding Pocket-Mediated Acquired and Intrinsic Azole Resistance in Fungal Pathogens

Examining Signatures of Natural Selection in Antifungal Resistance Genes Across Aspergillus Fungi

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