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

ABSTRACT: Newer fungal pathogens have emerged recently, attributed to their adaptation to higher environmental temperatures. With increasing earth’s temperatures, many existing fungal pathogens are adapting and show changes in host-pathogen interactions, disease pattern, and response to the antimicrobial drugs. Here, we show that thermal adaptation to 42C leads to reversible changes in fungal colony size, appearance, and azole drug response in human pathogenic fungus Aspergillus fumigatus. Importantly, this adaptation is mediated by a lncRNA, afu-182, whose RNA levels negatively correlate with temperature. Either growth back at lower temperature or ectopically increasing afu-182 RNA levels reverses the temperature adaptation. Global transcriptomic analyses show enrichment of pathogenesis associated genes at 37C and 42C compared to 25C. 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.

ORGANISM(S): Aspergillus fumigatus

PROVIDER: GSE319853 | GEO | 2026/03/02

REPOSITORIES: GEO