Aspergillus fumigatus has evolved numerous signal-transduction systems to sense and respond to stresses to survive and proliferate in harsh environmental conditions. Among these signal-transduction systems, the Ca2+ signaling pathway is one of most important response systems, which has been verified to be involved in stress adaptation. Fungal cytosolic Ca2+ concentrations are maintained at extreme low level to function as the second messenger while high concentrations of Ca2+ are immediately available for influx from outside of the cell into the cytoplasm and the intracellular Ca2+ stores. The Ca2+ channels, pumps, exchangers, and antiporters localized in the membrane as well as Ca2+ sensors with their signal effectors in the cytoplasm are highly networked to regulate, conduct and translate various signals. In this study, we demonstrate that the activation of the calcium signaling pathway induced by azole stress contributes to the survival of fungal cells during drug exposure. In contrast, the blocking of the calcium signaling pathway or the loss of the functional calcium signaling pathway components in A. fumigatus cause enhanced drug susceptibilities. Thus, effectively utilizing the inhibitors or blockers of the calcium signaling pathway might enhance the pharmacology of limited antifungal agents for azole resistance isolates in clinical A. fumigatus.
Full conference title:
- Fungal Genetics Conference 30th (2019)