Abstract
Aspergillus fumigatus is an airborne human fungal pathogen that can survive in a wide range of environmental condition. G protein complex transduces external signals from a variety of stimuli outside a cell to its interior effectors in all eukaryotes. Gβ-like CpcB (cross pathway control B) belongs to a WD40 repeat protein family with the conserved G–H and W–D residues. Previous studies have demonstrated that Gβ-like proteins cooperate with related signal transduction proteins to function during many important developmental processes in A. fumigatus. However, the molecular characteristics of Gβ-like CpcB have not yet been identified. In this study, we demonstrated that the G–H residues in WD repeat 1, 2, 3, and the W–D residue in WD repeat 2 of CpcB are required not only to control normal hyphal growth and conidiation but also to affect antifungal drug susceptibility. The enhanced drug resistance might be due to reduced intracellular drug accumulation and altered ergosterol component. Moreover, we find that the first G–H residue of CpcB plays an important role in the virulence of A. fumigatus. To our knowledge, this is the first report for finding the importance of the conserved G–H and W–D residues for a Gβ-like protein in understanding of G protein functions.
Highlights
Aspergillus fumigatus is a saprophytic fungus with a large number of buoyant airborne conidia, and it plays an essential role in carbon and nitrogen recycling due to its characteristic metabolic ability to assimilate organic carbon and some non-elemental sources of nitrogen (Tekaia and Latge, 2005; Lapp et al, 2014)
Based on the transcriptome analysis and drug susceptibility testing, we demonstrated that Gβ-like CpcB is involved in the maintenance of normal antifungal drug susceptibility, which is associated with the functions of necessary G–H and we substituted TrpAsp (W–D) residues
Bioinformatics analyses revealed that A. fumigatus CpcB contains the conserved G–H and W–D residues that are ubiquitous in WD family proteins
Summary
Aspergillus fumigatus is a saprophytic fungus with a large number of buoyant airborne conidia, and it plays an essential role in carbon and nitrogen recycling due to its characteristic metabolic ability to assimilate organic carbon and some non-elemental sources of nitrogen (Tekaia and Latge, 2005; Lapp et al, 2014). As an important opportunistic pathogen, A. fumigatus has become the most prevalent airborne fungal pathogen, causing severe and usually fatal invasive infections in immunocompromised hosts, especially individuals with cancer, leukemia, AIDS, organ transplantation, and chronic granulomatous disease (CGD). Previous studies have demonstrated that virulence determinants of A. fumigatus are multifactorial and are associated with the biological characteristics of the fungus and the immune status of the individual. Proteins involved in calcium signaling and G protein signaling, which play important roles in detecting and transmitting environmental signals, have been shown to be important for virulence (Abad et al, 2010)
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