Thermal adaptation cross-talks with azole response through lncRNA in Aspergillus fumigatus

Interestingly, we show that small heat shock proteins and chaperones, but not ATP dependent heat-shock proteins are negatively regulated by afu-182 at 37C and 42C. Previously, we have shown that delta afu-182 strain produce worse disease outcomes in a murine model of invasive pulmonary aspergilllosis. Here, more importantly, we show that overexpression of afu-182 in clinically azole resistant isolates increased survival in a murine model of invasive pulmonary aspergillosis.

Taken together, fungal adaptation to increased temperature leads to decrease in afu-182 RNA levels that is associated with worse disease outcomes upon azole treatment and an increase in MIC. This provides a framework, to take temperature into account when analyzing the rise in azole MIC in environmental and clinical isolates.