Crosstalk between Ca2+-signaling and the light-sensing pathway during stress responses and hyphal polar growth in Aspergillus nidulans and A. fumigatus

• Applicant: Professor Dr. Reinhard Fischer
• Subject Area: Metabolism, Biochemistry and Genetics of Microorganisms
• Term: from 2019 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 410129668

Aspergillus fumigatus is one of the most important airborne ascomycete pathogens and allergen worldwide. Several million people have invasive or chronic infections that lead to >600,000 deaths every year. Hence, a better understanding of the biology of this fungus may help to develop new or improve existing antifungal drugs in the future. Fungal pathogens must adapt to a variety of in vivo obstacles to survive. These obstacles include high temperature, pH variation, oxidative stress or plasma membrane's stress upon azole treatment. As other filamentous fungi, fungal pathogens have evolved numerous signal-transduction systems to sense and respond to environmental stresses to survive and proliferate in harsh environmental conditions. The HOG pathway and the Ca2+ signaling pathway both are involved in stress adaptations. Recently, it was discovered that phytochrome senses the light signal through the HOG pathway, and there is evidence in planta and in bacteria that phytochrome plays a role as molecular thermometer. In this proposal we hypothesize that phytochrome-dependent light sensing might be interlinked with Ca2+ signaling via the HOG pathway. We aim at characterizing the two signaling pathways in two related ascomycetes, Aspergillus nidulans and the opportunistic pathogenic A. fumigatus. Our preliminary data also indicate both phytochrome- and the Ca2+-signaling pathway are involved in thermo-sensing in A. nidulans. We plan to study the role of phytochrome, the HOG and the Ca2+ signaling pathway in temperature and azole antifungal sensing in A. nidulans and in A. fumigatus. The interaction between the two signaling pathways will be studied at the transcriptional and the posttranscriptional level. There is also good evidence that Ca2+ not only plays a role in stress adaptation, but also in polarized growth. It was shown that the concentration of Ca2+ oscillates during polar hyphal extension and that this oscillation may be responsible for oscillations of vesicle secretion and thus oscillatory growth of hyphae. Because stress responses cause dramatic changes of the intracellular Ca2+ concentration, effects of stress on polar cell extension are likely. To study this relationship, we are going to analyze how stress-response pathways affect hyphal polar growth in both fungi and how they affect virulence in A. fumigatus. For this aim, we will monitor the dynamics of the Ca2+ concentration in fungal cells expressing the calcium reporter aequorin combined with fluorescent protein GECO technologies and study the effect on vesicle traffic. We are going to apply super-resolution microscopy to visualize different vesicle populations in the hyphae and document their travel routes until fusion with the apical membrane.

• DFG Programme: Research Grants
• International Connection: China
• Partner Organisation: National Natural Science Foundation of China
• Cooperation Partner: Professorin Dr. Ling Lu