RT Journal Article
SR Electronic
T1 Comparative systems analysis of the secretome of the opportunistic pathogen <em>Aspergillus fumigatus</em> and other <em>Aspergillus</em> species
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 230953
DO 10.1101/230953
A1 R.P. Vivek-Ananth
A1 Karthikeyan Mohanraj
A1 Muralidharan Vandanashree
A1 Anupam Jhingran
A1 James P. Craig
A1 Areejit Samal
YR 2017
UL http://biorxiv.org/content/early/2017/12/08/230953.abstract
AB 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.