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

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.