Comparative systems analysis of the secretome of the opportunistic pathogen Aspergillus fumigatus and other Aspergillus species

Abstract

Aspergillus fumigatus and multiple other Aspergillus species cause a wide range of lung infections, collectively termed aspergillosis. Aspergilli are ubiquitous in environment with healthy immune systems routinely eliminating inhaled conidia, however, Aspergilli can become an opportunistic pathogen in immune-compromised patients. The aspergillosis mortality rate and emergence of drug-resistance reveals an urgent need to identify novel targets. Secreted and cell membrane proteins play a critical role in fungal-host interactions and pathogenesis. Using a computational pipeline integrating data from high-throughput experiments and bioinformatic predictions, we have identified secreted and cell membrane proteins in ten Aspergillus species known to cause aspergillosis. Small secreted and effector-like proteins similar to agents of fungal-plant pathogenesis were also identified within each secretome. A comparison with humans revealed that at least 70% of Aspergillus secretomes has no sequence similarity with the human proteome. An analysis of antigenic qualities of Aspergillus proteins revealed that the secretome is significantly more antigenic than cell membrane proteins or the complete proteome.Finally, overlaying an expression dataset, four A. fumigatus proteins upregulated during infection and with available structures, were found to be structurally similar to known drug target proteins in other organisms, and were able to dock in silico with the respective drug.

Exposure to the Pseudomonas aeruginosa secretome alters the proteome and secondary metabolite production of Aspergillus fumigatus

“…Aspergillus fumigatus is a ubiquitous saprophytic mould that releases airborne conidia, which may enter the human respiratory tract through inhalation. Many of the biological determinants that contribute to the ubiquity of the fungus in nature also play a role in establishing disease in humans and are associated with virulence and pathogenesis [1][2][3][4][5][6]. Among these attributes are the wide range of biosynthetic gene clusters (>30) responsible for the production of secondary metabolites that confer advantages to A. fumigatus in its natural habitat, including protection against UV stress, desiccation and competition with other microorganisms [7][8][9].…”