The role of Kdnase (sialidase) in cell wall integrity and virulence of Aspergillus fumigatus

Author: 
Date created: 
2018-08-17
Identifier: 
etd19771
Keywords: 
Aspergillus fumigatus
Sialidase
Kdnase
Amphotericin B
Cell wall
Virulence
Abstract: 

Aspergillus fumigatus is the leading airborne fungal pathogen worldwide. In immunocompromised individuals, exposure to conidiospores can lead to an infection known as invasive aspergillosis. We have previously shown that A. fumigatus possesses a sialidase that preferentially cleaves the sialic acid, Kdn (3-deoxy-d-glycero-d-galacto-2-nonulosonic acid) and is therefore a Kdnase. The purpose of my research was to characterize a Δkdnase knockout strain. Under hyperosmotic stress, cell wall α-glucan and chitin levels were significantly increased in Δkdnase hyphae compared to wild type (WT). Δkdnase was more susceptible to growth inhibition by amphotericin B and caspofungin but resistant to nikkomycin. Virulence of the Δkdnase strain in neutropenic mice was attenuated compared to WT when mice were also treated with amphotericin B, but not in the absence of the drug. uHPLC-MS analysis showed that WT and Δkdnase conidiospores, and WT hyphae contained Kdn; however, Kdn was not detectable in Δkdnase hyphae.

Document type: 
Thesis
Rights: 
This thesis may be printed or downloaded for non-commercial research and scholarly purposes. Copyright remains with the author.
File(s): 
Senior supervisor: 
Margo Moore
Department: 
Science: Biological Sciences Department
Thesis type: 
(Thesis) M.Sc.
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