Transcriptional Analysis Allows Genome Reannotation and Reveals that Cryptococcus gattii VGII Undergoes Nutrient Restriction during Infection

Cryptococcus gattii is a human and animal pathogen that infects healthy hosts and caused the Pacific Northwest outbreak of cryptococcosis. The inhalation of infectious propagules can lead to internalization of cryptococcal cells by alveolar macrophages, a niche in which C. gattii cells can survive a...

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Main Authors: Patrícia Aline Gröhs Ferrareze, Rodrigo Silva Araujo Streit, Patricia Ribeiro dos Santos, Francine Melise dos Santos, Rita Maria Cunha de Almeida, Augusto Schrank, Livia Kmetzsch, Marilene Henning Vainstein, Charley Christian Staats
Format: Article
Language:English
Published: MDPI AG 2017-08-01
Series:Microorganisms
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Online Access:https://www.mdpi.com/2076-2607/5/3/49
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author Patrícia Aline Gröhs Ferrareze
Rodrigo Silva Araujo Streit
Patricia Ribeiro dos Santos
Francine Melise dos Santos
Rita Maria Cunha de Almeida
Augusto Schrank
Livia Kmetzsch
Marilene Henning Vainstein
Charley Christian Staats
author_facet Patrícia Aline Gröhs Ferrareze
Rodrigo Silva Araujo Streit
Patricia Ribeiro dos Santos
Francine Melise dos Santos
Rita Maria Cunha de Almeida
Augusto Schrank
Livia Kmetzsch
Marilene Henning Vainstein
Charley Christian Staats
author_sort Patrícia Aline Gröhs Ferrareze
collection DOAJ
description Cryptococcus gattii is a human and animal pathogen that infects healthy hosts and caused the Pacific Northwest outbreak of cryptococcosis. The inhalation of infectious propagules can lead to internalization of cryptococcal cells by alveolar macrophages, a niche in which C. gattii cells can survive and proliferate. Although the nutrient composition of macrophages is relatively unknown, the high induction of amino acid transporter genes inside the phagosome indicates a preference for amino acid uptake instead of synthesis. However, the presence of countable errors in the R265 genome annotation indicates significant inhibition of transcriptomic analysis in this hypervirulent strain. Thus, we analyzed RNA-Seq data from in vivo and in vitro cultures of C. gattii R265 to perform the reannotation of the genome. In addition, based on in vivo transcriptomic data, we identified highly expressed genes and pathways of amino acid metabolism that would enable C. gattii to survive and proliferate in vivo. Importantly, we identified high expression in three APC amino acid transporters as well as the GABA permease. The use of amino acids as carbon and nitrogen sources, releasing ammonium and generating carbohydrate metabolism intermediaries, also explains the high expression of components of several degradative pathways, since glucose starvation is an important host defense mechanism.
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spelling doaj.art-b0cc39c4023b4043b823391b669727332022-12-22T01:31:49ZengMDPI AGMicroorganisms2076-26072017-08-01534910.3390/microorganisms5030049microorganisms5030049Transcriptional Analysis Allows Genome Reannotation and Reveals that Cryptococcus gattii VGII Undergoes Nutrient Restriction during InfectionPatrícia Aline Gröhs Ferrareze0Rodrigo Silva Araujo Streit1Patricia Ribeiro dos Santos2Francine Melise dos Santos3Rita Maria Cunha de Almeida4Augusto Schrank5Livia Kmetzsch6Marilene Henning Vainstein7Charley Christian Staats8Programa de Pós-Graduação em Biologia Celular e Molecular, Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul (UFRGS), 91501970 Porto Alegre, BrazilDepartamento de Biologia Molecular e Biotecnologia, Instituto de Biociências, Universidade Federal do Rio Grande do Sul (UFRGS), 91501970 Porto Alegre, BrazilPrograma de Pós-Graduação em Biologia Celular e Molecular, Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul (UFRGS), 91501970 Porto Alegre, BrazilPrograma de Pós-Graduação em Biologia Celular e Molecular, Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul (UFRGS), 91501970 Porto Alegre, BrazilInstituto de Física, Universidade Federal do Rio Grande do Sul (UFRGS), 91501970 Porto Alegre, BrazilPrograma de Pós-Graduação em Biologia Celular e Molecular, Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul (UFRGS), 91501970 Porto Alegre, BrazilPrograma de Pós-Graduação em Biologia Celular e Molecular, Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul (UFRGS), 91501970 Porto Alegre, BrazilPrograma de Pós-Graduação em Biologia Celular e Molecular, Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul (UFRGS), 91501970 Porto Alegre, BrazilPrograma de Pós-Graduação em Biologia Celular e Molecular, Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul (UFRGS), 91501970 Porto Alegre, BrazilCryptococcus gattii is a human and animal pathogen that infects healthy hosts and caused the Pacific Northwest outbreak of cryptococcosis. The inhalation of infectious propagules can lead to internalization of cryptococcal cells by alveolar macrophages, a niche in which C. gattii cells can survive and proliferate. Although the nutrient composition of macrophages is relatively unknown, the high induction of amino acid transporter genes inside the phagosome indicates a preference for amino acid uptake instead of synthesis. However, the presence of countable errors in the R265 genome annotation indicates significant inhibition of transcriptomic analysis in this hypervirulent strain. Thus, we analyzed RNA-Seq data from in vivo and in vitro cultures of C. gattii R265 to perform the reannotation of the genome. In addition, based on in vivo transcriptomic data, we identified highly expressed genes and pathways of amino acid metabolism that would enable C. gattii to survive and proliferate in vivo. Importantly, we identified high expression in three APC amino acid transporters as well as the GABA permease. The use of amino acids as carbon and nitrogen sources, releasing ammonium and generating carbohydrate metabolism intermediaries, also explains the high expression of components of several degradative pathways, since glucose starvation is an important host defense mechanism.https://www.mdpi.com/2076-2607/5/3/49Cryptococcus gattiiR265transcriptomegenomeannotationamino acidbronchoalveolar lavagecryptococcosis
spellingShingle Patrícia Aline Gröhs Ferrareze
Rodrigo Silva Araujo Streit
Patricia Ribeiro dos Santos
Francine Melise dos Santos
Rita Maria Cunha de Almeida
Augusto Schrank
Livia Kmetzsch
Marilene Henning Vainstein
Charley Christian Staats
Transcriptional Analysis Allows Genome Reannotation and Reveals that Cryptococcus gattii VGII Undergoes Nutrient Restriction during Infection
Microorganisms
Cryptococcus gattii
R265
transcriptome
genome
annotation
amino acid
bronchoalveolar lavage
cryptococcosis
title Transcriptional Analysis Allows Genome Reannotation and Reveals that Cryptococcus gattii VGII Undergoes Nutrient Restriction during Infection
title_full Transcriptional Analysis Allows Genome Reannotation and Reveals that Cryptococcus gattii VGII Undergoes Nutrient Restriction during Infection
title_fullStr Transcriptional Analysis Allows Genome Reannotation and Reveals that Cryptococcus gattii VGII Undergoes Nutrient Restriction during Infection
title_full_unstemmed Transcriptional Analysis Allows Genome Reannotation and Reveals that Cryptococcus gattii VGII Undergoes Nutrient Restriction during Infection
title_short Transcriptional Analysis Allows Genome Reannotation and Reveals that Cryptococcus gattii VGII Undergoes Nutrient Restriction during Infection
title_sort transcriptional analysis allows genome reannotation and reveals that cryptococcus gattii vgii undergoes nutrient restriction during infection
topic Cryptococcus gattii
R265
transcriptome
genome
annotation
amino acid
bronchoalveolar lavage
cryptococcosis
url https://www.mdpi.com/2076-2607/5/3/49
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