Exposure of Aspergillus fumigatus to methylprednisolone results in increased expression of cell wall genes associated with virulence

Ref ID: 19182

Author:

E. Bathoorn*, P. Krijgsheld, S. Braem, G.J. van Veluw, J. Van strijp, H.A.B. Wosten, P.-J. Haas

Author address:

Utrecht, NL

Full conference title:

23rd European Congress of Clinical Microbiology and
Infectious Diseases

Date: 27 April 2014

Abstract:

Objectives: Treatment with corticosteroids is associated with increased risk on invasive aspergillosis. We have found that exposure to methylprednisolone (MP) causes a phenotypic change in Aspergillus fumigatus 293 (AF293) growth. Effects of MP on AF293 whole genome mRNA expression were assessed to identify molecular pathways by which it acts. Cell wall associated genes encoding for hydrophobin, melanin, galactomannan, and ergosterol were of specific interest to explain the phenotypic change.
Methods: Liquid submerged cultures were incubated for 8 hours with 8×106 AF293 spores ml-1 in complete medium at 37°C, with and without the addition of 1 µM MP. RNA of AF293 was isolated and used for RNA sequencing. T-tests were performed on mean reads per kb per Million reads of triplicate experiments in both groups (p <=0.05, FDR<= 0.01). Genes were regarded as differentially expressed genes (DEGs) when the average 2log mean value was > 1, or < -1. An hypergeometric test (with Bonferroni corrected p-value <= 0.05) was used to find significantly enriched GO terms in DEGs compared to the genome background. Results: In total, 9,030 different transcripts of AF293 genes were expressed of the 9,887 described; 400 were upregulated, and 502 downregulated DEGs in MP treated AF293. GO analysis showed overrepresentation of upregulated genes annotated to oxidoreductase reactivity, iron ion binding, cell wall structure, and organic substance transport. Four of 4 genes encoding for hydrophobins were differentially upregulated in MP treated AF293, including rodA and rodB. In addition, 3 of 6 genes involved in melanin synthesis were differentially expressed. Of these, 2 were upregulated DEGs (arp1 and arp2), and 1 was a down-regulated DEG (ayg1). We detected 3 genes involved in galactomannan expression: Galactomannoprotein Man Pol1, and antigenic cell wall galactomannoprotein were upregulated DEGs; OCH1 was indifferently expressed. None of 13 annotated genes to ergosterol synthesis were DEGs. Conclusion: Exposure of AF293 to MP causes changes in cell wall structure by upregulation of hydrophobin, melanin, and galactomannan genes. These genes are associated with virulence, and defence against oxidative stress and toxic compounds. Future experiments using functional assays will give insight in the clinical relevance of these results.

Abstract Number: P1088

Conference Year: 2013

Link to conference website: http://registration.akm.ch/einsicht.php?XNABSTRACT_ID=164313&XNSPRACHE_ID=2&XNKONGRESS_ID=180&XNMASK

New link: NULL

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