Modification of exopolysaccharide composition can increase the virulence of non -pathogenic Aspergillus species

Ref ID: 19591

Author:

MJ Lee1*, H Liu2, Q Al Abdallah1, BD Snarr1, FN Gravelat1, T Xiao1, SGW Kaminskyj3,
CA Piccirillo1, MC Guiot4, JP Latgé5, T Fontaine5, SG Filler2,6, DC Sheppard1,7

Author address:

1Microbiology and Immunology, McGill University, Montreal, Canada
2Division of Infectious Diseases, LA Biomed-UCLA, Torrance, USA
3Biology, University of Saskatchewan, Saskatoon, Canada
4Pathology, Montreal Neurological Institute, Montreal, Canada

Full conference title:

6th Advances Against Aspergillosis 2014

Abstract:

Purpose:
Differences in the composition or quantity of Aspergillus nidulans galactosaminogalactan may
contribute to the reduced virulence of this organism
Methods:
Gene transcript levels were measured by real-time RT-PCR. Galactosaminogalactan production
and composition, adherence to polystyrene, cell wall morphology, β -glucan masking property,
and ability to induce apoptosis were assayed. Strains of A. nidulans that heterologously expressed
A. fumigatus uge3 (An-Uge3) or overexpressed A. nidulans ugeB (An-UgeB) were constructed. The
virulence of A. fumigatus Af293 and the various A. nidulans strains was assessed in mice that were
immunosuppressed with either cortisone acetate alone or cortisone acetate plus cyclophosphamide.
The mice were inoculated intranasally with 106 conidia per strain. Virulence was assessed by survival
and histopathologic analysis of the infected lungs.
Results:
Wild-type A. fumigatus and A. nidulans produced similar levels of galactosaminogalactan, however
the GalNAc to galactose ratio was markedly reduced in A. nidulans. A. nidulans expression of
ugeB was considerably lower than A. fumigatus expression of uge3. Both An-Uge3 and An-UgeB
strains had increased production of galactosaminogalactan, which had a higher GalNAc content.
The control strain of A. nidulans had low adherence to polystyrene and poor induction of leukocyte
apoptosis, as compared to wild-type A. fumigatus. However, the An-Uge3 and An-UgeB strains
adhered to polystryine and induced leukocyte apoptosis similarly to A. fumigatus. Both the An-Uge3
and An-UgeB strains had significantly increased virulence in corticosteroid treated, non-neutropenic
mice, and the virulence of these strains was similar to A. fumigatus. Histologic examination of the
infected lungs showed an increase in lesion size and invasion in mice infected with An-Uge3. In
contrast, the virulence of the An-Uge3 and An-UgeB strains in leukopenic mice was similar to wildtype
A. nidulans, suggesting that the increased virulence of these strains is mediated through effects
of galactosaminogalactan on leukocytes.
Conclusion:
Our results demonstrate that one mechanism for the low virulence of A. nidulans is that the
galactosaminogalactan produced by this organism is significantly different from that produced by
the more pathogenic A. fumigatus. Furthemore, these data provide additional support for the key role
of galactosaminogalactan in adherence, host cell interactions, and virulence of A. fumigatus.

NOTE: THIS ABSTRACT HAS BEEN SELECTED FOR ORAL PRESENTATION.

Abstract Number: 116

Conference Year: 2014

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

New link: NULL

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