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Systemic Approach to Virulence Gene Network Analysis for Gaining New Insight into Cryptococcal Virulence
Cryptococcus neoformans is pathogenic yeast, responsible for highly lethal infections in compromised patients around the globe. C. neoformans typically initiates infections in mammalian lung tissue and subsequently disseminates to the central nervous system where it causes significant pathologies. V...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5081415/ https://www.ncbi.nlm.nih.gov/pubmed/27833589 http://dx.doi.org/10.3389/fmicb.2016.01652 |
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author | Malachowski, Antoni N. Yosri, Mohamed Park, Goun Bahn, Yong-Sun He, Yongqun Olszewski, Michal A. |
author_facet | Malachowski, Antoni N. Yosri, Mohamed Park, Goun Bahn, Yong-Sun He, Yongqun Olszewski, Michal A. |
author_sort | Malachowski, Antoni N. |
collection | PubMed |
description | Cryptococcus neoformans is pathogenic yeast, responsible for highly lethal infections in compromised patients around the globe. C. neoformans typically initiates infections in mammalian lung tissue and subsequently disseminates to the central nervous system where it causes significant pathologies. Virulence genes of C. neoformans are being characterized at an increasing rate, however, we are far from a comprehensive understanding of their roles and genetic interactions. Some of these reported virulence genes are scattered throughout different databases, while others are not yet included. This study gathered and analyzed 150 reported virulence associated factors (VAFs) of C. neoformans. Using the web resource STRING database, our study identified different interactions between the total VAFs and those involved specifically in lung and brain infections and identified a new strain specific virulence gene, SHO1, involved in the mitogen-activated protein kinase signaling pathway. As predicted by our analysis, SHO1 expression enhanced C. neoformans virulence in a mouse model of pulmonary infection, contributing to enhanced non-protective immune Th2 bias and progressively enhancing fungal growth in the infected lungs. Sequence analysis indicated 77.4% (116) of total studied VAFs are soluble proteins, and 22.7% (34) are transmembrane proteins. Motifs involved in regulation and signaling such as protein kinases and transcription factors are highly enriched in Cryptococcus VAFs. Altogether, this study represents a pioneering effort in analysis of the virulence composite network of C. neoformans using a systems biology approach. |
format | Online Article Text |
id | pubmed-5081415 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-50814152016-11-10 Systemic Approach to Virulence Gene Network Analysis for Gaining New Insight into Cryptococcal Virulence Malachowski, Antoni N. Yosri, Mohamed Park, Goun Bahn, Yong-Sun He, Yongqun Olszewski, Michal A. Front Microbiol Microbiology Cryptococcus neoformans is pathogenic yeast, responsible for highly lethal infections in compromised patients around the globe. C. neoformans typically initiates infections in mammalian lung tissue and subsequently disseminates to the central nervous system where it causes significant pathologies. Virulence genes of C. neoformans are being characterized at an increasing rate, however, we are far from a comprehensive understanding of their roles and genetic interactions. Some of these reported virulence genes are scattered throughout different databases, while others are not yet included. This study gathered and analyzed 150 reported virulence associated factors (VAFs) of C. neoformans. Using the web resource STRING database, our study identified different interactions between the total VAFs and those involved specifically in lung and brain infections and identified a new strain specific virulence gene, SHO1, involved in the mitogen-activated protein kinase signaling pathway. As predicted by our analysis, SHO1 expression enhanced C. neoformans virulence in a mouse model of pulmonary infection, contributing to enhanced non-protective immune Th2 bias and progressively enhancing fungal growth in the infected lungs. Sequence analysis indicated 77.4% (116) of total studied VAFs are soluble proteins, and 22.7% (34) are transmembrane proteins. Motifs involved in regulation and signaling such as protein kinases and transcription factors are highly enriched in Cryptococcus VAFs. Altogether, this study represents a pioneering effort in analysis of the virulence composite network of C. neoformans using a systems biology approach. Frontiers Media S.A. 2016-10-27 /pmc/articles/PMC5081415/ /pubmed/27833589 http://dx.doi.org/10.3389/fmicb.2016.01652 Text en Copyright © 2016 Malachowski, Yosri, Park, Bahn, He and Olszewski. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Microbiology Malachowski, Antoni N. Yosri, Mohamed Park, Goun Bahn, Yong-Sun He, Yongqun Olszewski, Michal A. Systemic Approach to Virulence Gene Network Analysis for Gaining New Insight into Cryptococcal Virulence |
title | Systemic Approach to Virulence Gene Network Analysis for Gaining New Insight into Cryptococcal Virulence |
title_full | Systemic Approach to Virulence Gene Network Analysis for Gaining New Insight into Cryptococcal Virulence |
title_fullStr | Systemic Approach to Virulence Gene Network Analysis for Gaining New Insight into Cryptococcal Virulence |
title_full_unstemmed | Systemic Approach to Virulence Gene Network Analysis for Gaining New Insight into Cryptococcal Virulence |
title_short | Systemic Approach to Virulence Gene Network Analysis for Gaining New Insight into Cryptococcal Virulence |
title_sort | systemic approach to virulence gene network analysis for gaining new insight into cryptococcal virulence |
topic | Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5081415/ https://www.ncbi.nlm.nih.gov/pubmed/27833589 http://dx.doi.org/10.3389/fmicb.2016.01652 |
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