RT Journal Article
SR Electronic
T1 Genomic and phenotypic heterogeneity of clinical isolates of the human pathogens <em>Aspergillus fumigatus, Aspergillus lentulus</em> and <em>Aspergillus fumigatiaffinis</em>
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.02.28.970384
DO 10.1101/2020.02.28.970384
A1 Renato Augusto Corrêa dos Santos
A1 Jacob L. Steenwyk
A1 Olga Rivero-Menendez
A1 Matthew E. Mead
A1 Lilian Pereira Silva
A1 Rafael Wesley Bastos
A1 Ana Alastruey-Izquierdo
A1 Gustavo Henrique Goldman
A1 Antonis Rokas
YR 2020
UL http://biorxiv.org/content/early/2020/02/28/2020.02.28.970384.abstract
AB Fungal pathogens are a global threat to human health. For example, fungi from the genus Aspergillus cause a spectrum of diseases collectively known as aspergillosis. Most of the &gt;200,000 life-threatening aspergillosis infections per year worldwide are caused by Aspergillus fumigatus. Recently, molecular typing techniques have revealed that aspergillosis can also be caused by organisms that are phenotypically similar to A. fumigatus but genetically distinct, such as Aspergillus lentulus and Aspergillus fumigatiaffinis. Importantly, some of these so-called cryptic species exhibit different virulence and drug susceptibility profiles than A. fumigatus, however, our understanding of their biology and pathogenic potential has been stymied by the lack of genome sequences and phenotypic profiling. To fill this gap, we phenotypically characterized the virulence and drug susceptibility of 15 clinical strains of A. fumigatus, A. lentulus, and A. fumigatiaffinis from Spain and sequenced their genomes. We found heterogeneity in virulence and drug susceptibility across species and strains. Genes known to influence drug susceptibility (cyp51A and fks1) vary in paralog number and sequence among these species and strains and correlate with differences in drug susceptibility. Similarly, genes known to be important for virulence in A. fumigatus showed variability in number of paralogs across strains and across species. Characterization of the genomic similarities and differences of clinical strains of A. lentulus, A. fumigatiaffinis, and A. fumigatus that vary in disease-relevant traits will advance our understanding of the variance in pathogenicity between Aspergillus species and strains that are collectively responsible for the vast majority of aspergillosis infections in humans.