ORCID Profile
0000-0002-2986-350X
Current Organisations
Universidade de São Paulo - Faculdade de Ciências Farmacêuticas
,
Universidade de São Paulo
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Publisher: Cold Spring Harbor Laboratory
Date: 20-04-2021
DOI: 10.1101/2021.04.19.440431
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 lification 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.
Publisher: Springer Science and Business Media LLC
Date: 2006
DOI: 10.1038/NATURE04572
Publisher: Public Library of Science (PLoS)
Date: 2022
DOI: 10.1371/JOURNAL.PGEN.1010001
Abstract: Invasive Pulmonary Aspergillosis, which is caused by the filamentous fungus Aspergillus fumigatus , is a life-threatening infection for immunosuppressed patients. Chromatin structure regulation is important for genome stability maintenance and has the potential to drive genome rearrangements and affect virulence and pathogenesis of pathogens. Here, we performed the first A . fumigatus global chromatin profiling of two histone modifications, H3K4me3 and H3K9me3, focusing on the two most investigated A . fumigatus clinical isolates, Af293 and CEA17. In eukaryotes, H3K4me3 is associated with active transcription, while H3K9me3 often marks silent genes, DNA repeats, and transposons. We found that H3K4me3 deposition is similar between the two isolates, while H3K9me3 is more variable and does not always represent transcriptional silencing. Our work uncovered striking differences in the number, locations, and expression of transposable elements between Af293 and CEA17, and the differences are correlated with H3K9me3 modifications and higher genomic variations among strains of Af293 background. Moreover, we further showed that the Af293 strains from different laboratories actually differ in their genome contents and found a frequently lost region in chromosome VIII. For one such Af293 variant, we identified the chromosomal changes and demonstrated their impacts on its secondary metabolites production, growth and virulence. Overall, our findings not only emphasize the influence of genome heterogeneity on A . fumigatus fitness, but also caution about unnoticed chromosomal variations among common laboratory strains.
Publisher: Informa UK Limited
Date: 02-01-2016
Location: Brazil
Location: Brazil
No related grants have been discovered for Gustavo Goldman.