Proteome Analysis of Human Lung Epithelial Cells Interacting with Aspergillus Terreus Conidia and Structure Function Relation of nsSNPs in Innate Immune Receptors

Abstract

The life-cycle of filamentous fungi consists of conidia, germinating conidia, hyphae and mycelium. Recently, filamentous fungus has gained importance among the opportunistic fungal pathogens. Germination is the key event in life-cycle of the filamentous fungus including Aspergillus species. The germination of the conidia in Aspergillus species is critical to establish invasive infections in immunocompromised individuals. Inhaled conidia often cause hypersensitive complications in immunocompetent host. Various studies using transcriptomic and proteomic approaches have been carried out to elucidate the biochemical pathways associated with germination. Such studies revealed that multiple genes and their products are active during germination of conidia in fungal system. However, Aspergillus species lack such studies at different conditions, morphological forms etc. Thus, objective (first) of current study was to establish a global proteome profile of germinating conidia of Aspergillus terreus. Our study reports proteins involved in translation, carbohydrate metabolism and transport that suggest their association during germination. Also, high expression of terrelysin in germination conidia may help to propose A. terreus specific diagnosis. Further, identification of proteins that are associated with mycotoxins production suggests their role in invasion of host tissues. The second objective of study was to explore the global proteome analysis of human lung epithelial cells (A549) during its interaction with conidia, as epithelial cells are the primary defense cells encountered by inhaled conidia. Interaction studies showed expressed proteins were involved in internalization of conidia or in immune response through Nuclear Factor-kB pathway. This pathway stimulates the production of IL-8 and, thus, could be evaluated further for biomarker target to control inflammation during lung infections. The third objective of current study was to predict the deleterious effect of non-synonymous SNPs on innate immune receptors su