Proteome Profile of Aspergillus terreus Conidia at Germinating Stage: Identification of Probable Virulent Factors and Enzymes from Mycotoxin Pathways

Abstract

Aspergillus terreus is an emerging opportunistic fungal pathogen that causes invasive aspergillosis in immunocompromised individuals. The main risk group of individuals for this organism is leukopenic patients, individuals having cancers, bone marrow transplant persons and those who have immunological disorders. The lack of early diagnostic marker for A. terreus and intrinsic resistance to Amphotericin B, further limits the successful therapy of A. terreus-associated infections. The germination of inhaled conidia is the key step to establish successful invasion in host tissues or organs. Thus, profiling of expressed proteins during germination of conidia not only shed light on proteins that are involved in invasion or virulence but may also provide early diagnostic markers. We used nanoLC-Q-TOF to study the proteome of germinating conidia (at 16 h time points) of A. terreus. We observed expression of 373 proteins in germinating conidia of A. terreus. A total of 74 proteins were uncharacterized in the database. The expressed proteins were associated with various processes like cell wall modulation, virulence factors and secondary metabolite biosynthesis. The most abundant proteins were associated with protein biosynthesis, carbohydrate metabolism and unknown functions. Among virulent proteins, mitogen-activated protein kinase (hog1) and mitogen-activated protein kinase (mpkC) are key virulent proteins observed in our study. We observed 7 enzymes from terretonin and 10 enzymes from geodin mycotoxin biosynthesis pathway. Interestingly, we observed expression of terrelysin protein, associated with blood cell lysis. Quantitative RT-PCR analysis showed 26-fold increase in transcripts encoding for dihydrogeodin oxidase and 885-fold for terrelysin gene in germinating conidia in comparison to conidia. Further, we propose that terrelysin protein and secondary metabolite such as geodin could be explored as diagnostic marker for A. terreus-associated infections.