COMPARATIVE GENOME ANALYSIS OF ASPERGILLUS TANNERI, A. FUMIGATUS, A. PARASITICUS, AND A. FLAVUS PREDICTS MECHANISMS OF DIFFERENTIAL HOST VIRULENCE

Ref ID: 19618

Author:

L Losada1*, J Sugui2, N Zafar1, V Joardar1, S Pakala1, J Yu3, K Ehrlich3, D Bhatnagar3, JK Chung2,
WC Nierman1

Author address:

1Infectious Diseases, The J. Craig Venter Institute, Rockville, MD, USA
2Molecular Microbiology Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy
and Infectious Diseases, National Institutes of Health, MD, USA
3Foo

Full conference title:

6th Advances Against Aspergillosis 2014

Abstract:

Purpose:
The genus Aspergillus is responsible for several respiratory conditions among them invasive
aspergillosis (IA). In the United States, IA is usually caused by A. fumigatus, while A. flavus represents
a very small fraction of IA cases. Recently, we described a novel, highly virulent, aggressively
invasive, and drug resistant species, Aspergillus tanneri. We sought to understand the differences in
virulence in these three species by performing comparative genomics analysis.
Methods:
To this end, we sequenced the genomes of A. tanneri, an additional strain of A. flavus, AF70, and
a strain of A. parasiticus, a species not known to cause IA using the paired-end Illumina GAIIx or
HiSeq platrorms coupled with 5 KB paired-end libraries for improved scaffolding. Assemblies were
carried out using Celera Assembler.
Results:
The genomes of A. tanneri and AF70 were assembled into 1715 and 1139 scaffolds, totaling 36.5Mb
and 37.2Mb. A. tannerii contained 11,112 predicted protein coding genes. The ’core’ genome of these
aspergilli consisted of 5,834 genes, which means that greater than 50% of genes in A. fumigatus are
shared with a divergent group of aspergilli. An additional 1,462 genes were shared between 7 out of
8 genomes, in which most cases, Atan did not have an ortholog. Genomic analysis showed that Atan
was no more similar to A. flavus than to A. fumigatus indicating that it is a distinct pathogenic lineage
within the aspergilli. Comparative genomics showed that over 5,600 genes were unique to A. flavus
strains compared to other aspergilli. Nearly 500 of these genes were unique to either A. flavus 3357 or
AF70 alone. In contrast, A. tanneri had over 2,400 unique genes, which corresponds to roughly 20%
of its genome. Among the unique genes in each species were several clusters that encode for nonribosomal
peptide synthases and polyketide synthases, suggesting that novel secondary metabolites
may play a role in virulence. When analyzed using SMURF to identify secondary metabolite clusters,
Atan was predicted to have almost 3 times as many clusters (73 total) as A. flavus or A. fumigatus. A
more in-depth comparison of potential virulence traits including proteases, allergens, and metabolic
versatility, especially in comparison with the non-human pathogen A. parasiticus will be presented.
Conclusions:
We have sequenced important members of the Aspergillus genus and conducted comparative
genomic analysis. The results show a remarkable number of core genes among aspergilli – over
50% of their genomes – even across very distant relatives. The results from this study can be used
to explore genetic differences that might explain phenotypic differences including drug resistance,
host range, and virulence.

Abstract Number: 143

Conference Year: 2014

Link to conference website: http://www.AAA2014.org

New link: NULL

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