The sino-nasal warzone: transcriptomic and genomic studies on sino-nasal aspergillosis in dogs

Abstract

We previously showed that each dog with chronic non-invasive sino-nasal aspergillosis (SNA) was infected with a single genotype of Aspergillus fumigatus. Here, we studied the transcriptome of this fungal pathogen and the canine host within the biofilm resulting from the infection. We describe here transcriptomes resulting from natural infections in animal species with A. fumigatus. The host transcriptome showed high expression of IL-8 and alarmins, uncontrolled inflammatory reaction and dysregulation of the Th17 response. The fungal transcriptome showed in particular expression of genes involved in secondary metabolites and nutrient acquisition. Single-nucleotide polymorphism analysis of fungal isolates from the biofilms showed large genetic variability and changes related with adaptation to host environmental factors. This was accompanied with large phenotypic variability in in vitro stress assays, even between isolates from the same canine patient. Our analysis provides insights in genetic and phenotypic variability of Aspergillus fumigatus in biofilms of naturally infected dogs reflecting in-host adaptation. Absence of a Th17 response and dampening of the Th1 response contributes to the formation of a chronic sino-nasal warzone.

Growth of Aspergillus fumigatus in Biofilms in Comparison to Candida albicans

“…In the study of Bertuzzi et al [112] it was observed that the zinc transporter ZrfB (Afu2g03860) was downregulated under neutral-alkaline conditions via PacC (Afu3g11970), suggesting that A. fumigatus biofilms are neutral to alkaline. Interestingly, mature biofilms in dogs suffering from sino-nasal aspergillosis (SNA) have an elevated pH of around 8 [89]. In agreement with this, it was found that the ZrfC (Afu4g09560) zinc transporter was also expressed in biofilms in SNA, which is required for zinc acquisition under alkaline conditions [115].…”

“…Gliotoxin, for example, is an important molecule in the regulation of the host response via several mechanisms, for example the induction of apoptosis in leukocytes and the inhibition of T-cell and B-cells response [107]. Interestingly, expression of the gliotoxin and hexadehydro-astechrome clusters was also detected in mature biofilms in dogs suffering from sino-nasal aspergillosis (SNA) [89], underscoring the important role of these secondary metabolites for A. fumigatus growing in biofilm.…”

“…A study by Valdes et al [89] investigated whether A. fumigatus was also able to acquire mutations in the case of long-term exposure to the sino-nasal environment of dogs. Through whole genome sequencing, single-nucleotide polymorphisms (SNPs) were identified in isolates from dogs suffering from sino-nasal aspergillosis.…”

Assessment of the nasal microbiota in dogs with fungal rhinitis before and after cure and in dogs with chronic idiopathic rhinitis.

“…Fungal rhinitis secondary to infection with Aspergillus fumigatus is a common cause of nasal disease in dogs while it is uncommon in humans. Why young otherwise healthy dolichocephalic dogs have their nasal cavity and sinus invaded by the fungus is not yet totally understood, despite extensive investigation [13][14][15] . Local dysimmunity is suspected, which associates a host response, consisting in Th1 and in ammatory response 16,17 with an in-host adaptive genetic and phenotypic response of the fungus itself, enabling growth of the pathogen and contributing to the suppression of the host immune response 15,18 .…”

Assessment of the nasal microbiota in dogs with fungal rhinitis before and after cure and in dogs with chronic idiopathic rhinitis

“…Fungal rhinitis secondary to infection with Aspergillus fumigatus is a common cause of nasal disease in dogs while it is uncommon in humans. Why young otherwise healthy dolichocephalic dogs have their nasal cavity and sinus invaded by the fungus is not yet totally understood, despite extensive investigation [ 13 – 15 ]. The host itself but also the fungus have been described as contributing to local dysimmunity.…”