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...

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Autores principales:	R. P. Vivek-Ananth, Karthikeyan Mohanraj, Muralidharan Vandanashree, Anupam Jhingran, James P. Craig, Areejit Samal
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/16d32d433ac243b4ae647a142c4ef9a7
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spelling	oai:doaj.org-article:16d32d433ac243b4ae647a142c4ef9a72021-12-02T15:07:44ZComparative systems analysis of the secretome of the opportunistic pathogen Aspergillus fumigatus and other Aspergillus species10.1038/s41598-018-25016-42045-2322https://doaj.org/article/16d32d433ac243b4ae647a142c4ef9a72018-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25016-4https://doaj.org/toc/2045-2322Abstract 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 have 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.R. P. Vivek-AnanthKarthikeyan MohanrajMuralidharan VandanashreeAnupam JhingranJames P. CraigAreejit SamalNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-16 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q R. P. Vivek-Ananth Karthikeyan Mohanraj Muralidharan Vandanashree Anupam Jhingran James P. Craig Areejit Samal Comparative systems analysis of the secretome of the opportunistic pathogen Aspergillus fumigatus and other Aspergillus species
description	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 have 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.
format	article
author	R. P. Vivek-Ananth Karthikeyan Mohanraj Muralidharan Vandanashree Anupam Jhingran James P. Craig Areejit Samal
author_facet	R. P. Vivek-Ananth Karthikeyan Mohanraj Muralidharan Vandanashree Anupam Jhingran James P. Craig Areejit Samal
author_sort	R. P. Vivek-Ananth
title	Comparative systems analysis of the secretome of the opportunistic pathogen Aspergillus fumigatus and other Aspergillus species
title_short	Comparative systems analysis of the secretome of the opportunistic pathogen Aspergillus fumigatus and other Aspergillus species
title_full	Comparative systems analysis of the secretome of the opportunistic pathogen Aspergillus fumigatus and other Aspergillus species
title_fullStr	Comparative systems analysis of the secretome of the opportunistic pathogen Aspergillus fumigatus and other Aspergillus species
title_full_unstemmed	Comparative systems analysis of the secretome of the opportunistic pathogen Aspergillus fumigatus and other Aspergillus species
title_sort	comparative systems analysis of the secretome of the opportunistic pathogen aspergillus fumigatus and other aspergillus species
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/16d32d433ac243b4ae647a142c4ef9a7
work_keys_str_mv	AT rpvivekananth comparativesystemsanalysisofthesecretomeoftheopportunisticpathogenaspergillusfumigatusandotheraspergillusspecies AT karthikeyanmohanraj comparativesystemsanalysisofthesecretomeoftheopportunisticpathogenaspergillusfumigatusandotheraspergillusspecies AT muralidharanvandanashree comparativesystemsanalysisofthesecretomeoftheopportunisticpathogenaspergillusfumigatusandotheraspergillusspecies AT anupamjhingran comparativesystemsanalysisofthesecretomeoftheopportunisticpathogenaspergillusfumigatusandotheraspergillusspecies AT jamespcraig comparativesystemsanalysisofthesecretomeoftheopportunisticpathogenaspergillusfumigatusandotheraspergillusspecies AT areejitsamal comparativesystemsanalysisofthesecretomeoftheopportunisticpathogenaspergillusfumigatusandotheraspergillusspecies
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Comparative systems analysis of the secretome of the opportunistic pathogen Aspergillus fumigatus and other Aspergillus species

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