Chromatin profiling reveals genome stability heterogeneity in clinical isolates of the human pathogen Aspergillus fumigatus

Abstract

Invasive Pulmonary aspergillosis is a life-threatening infection in immunosuppressed patients caused by the filamentous fungus Aspergillus fumigatus. Chromatin structure regulation is important for genome stability maintenance and has the potential to lead to genome rearrangements driving differences in virulence and pathogenesis of different A. fumigatus isolates. Here, we compared the chromatin activities of the most investigated clinical isolates Af293 and CEA17 and uncovered striking differences in the number, locations and expression of transposable elements. We found evidence for higher genome instability in Af293 as compared to CEA17 and identified a spontaneous Af293 variant that exhibits gross chromosomal alterations including the loss of a 320 kb long segment in chromosome VIII and the amplification of a biosynthetic gene cluster. As a consequence of these re-arrangements, the variant shows increased secondary metabolites production, growth and virulence. Our work emphasizes genome stability heterogeneity as an evolutionary driver of A. fumigatus fitness and virulence.

Aspergillus fumigatus FhdA Transcription Factor Is Important for Mitochondrial Activity and Codon Usage Regulation during the Caspofungin Paradoxical Effect

“…The copyright holder for this preprint (which this version posted May 25, 2022. ; https://doi.org/10.1101/2022.05.21.492902 doi: bioRxiv preprint control (Figure 1D, upper panel), while the 234 genes bound after CSP exposure are mostly involved in amino acid metabolism (Figure 1D, bottom panel). Of the 122 constitutive targets of FhdA, 15 have no feature, 29 encode proteins, 43 overlap with intergenic regions bound by the modified histone H3K9me3 previously described by our group (9), and 35 encode tRNAs (Figure 1E).…”

Aspergillus fumigatus FhdA transcription factor is important for mitochondrial activity and codon usage regulation during the caspofungin paradoxical effect

“…Enrichment analysis of the 778 genes bound by FhdA in control conditions suggest that this TF is involved in regulation of processes related to gene expression and transcriptional control (Figure 1D, upper panel), while the 234 genes bound after CSP exposure are mostly involved in amino acid metabolism (Figure 1D, bottom panel). Of the 122 constitutive targets of FhdA, 15 have no feature, 29 encode proteins, 43 overlap with intergenic regions bound by the modified histone H3K9me3 previously described by our group (9), and 35 encode tRNAs (Figure 1E).…”