Cargando…

RgsA Attenuates the PKA Signaling, Stress Response, and Virulence in the Human Opportunistic Pathogen Aspergillus fumigatus

The regulator of G-protein signaling (RGS) proteins play an important role in upstream control of heterotrimeric G-protein signaling pathways. In the genome of the human opportunistic pathogenic fungus Aspergillus fumigatus, six RGS protein-encoding genes are present. To characterize the rgsA gene p...

Descripción completa

Detalles Bibliográficos
Autores principales: Lwin, Hnin Phyu, Choi, Yong-Ho, Lee, Min-Woo, Yu, Jae-Hyuk, Shin, Kwang-Soo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6888639/
https://www.ncbi.nlm.nih.gov/pubmed/31717953
http://dx.doi.org/10.3390/ijms20225628
_version_ 1783475278067007488
author Lwin, Hnin Phyu
Choi, Yong-Ho
Lee, Min-Woo
Yu, Jae-Hyuk
Shin, Kwang-Soo
author_facet Lwin, Hnin Phyu
Choi, Yong-Ho
Lee, Min-Woo
Yu, Jae-Hyuk
Shin, Kwang-Soo
author_sort Lwin, Hnin Phyu
collection PubMed
description The regulator of G-protein signaling (RGS) proteins play an important role in upstream control of heterotrimeric G-protein signaling pathways. In the genome of the human opportunistic pathogenic fungus Aspergillus fumigatus, six RGS protein-encoding genes are present. To characterize the rgsA gene predicted to encode a protein with an RGS domain, we generated an rgsA null mutant and observed the phenotypes of the mutant. The deletion (Δ) of rgsA resulted in increased radial growth and enhanced asexual sporulation in both solid and liquid culture conditions. Accordingly, transcripts levels of the key asexual developmental regulators abaA, brlA, and wetA are elevated in the ΔrgsA mutant. Moreover, ΔrgsA resulted in elevated spore germination rates in the absence of a carbon source. The activity of cAMP-dependent protein kinase A (PKA) and mRNA levels of genes encoding PKA signaling elements are elevated by ΔrgsA. In addition, mRNA levels of genes associated with stress-response signaling increased with the lack of rgsA, and the ΔrgsA spores showed enhanced tolerance against oxidative stressors. Comparative transcriptomic analyses revealed that the ΔrgsA mutant showed higher mRNA levels of gliotoxin (GT) biosynthetic genes. Accordingly, the rgsA null mutant exhibited increased production of GT and elevated virulence in the mouse. Conversely, the majority of genes encoding glucan degrading enzymes were down-regulated by ΔrgsA, and endoglucanase activities were reduced. In summary, RgsA plays multiple roles, governing growth, development, stress responses, virulence, and external polymer degradation—likely by attenuating PKA signaling.
format Online
Article
Text
id pubmed-6888639
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-68886392019-12-09 RgsA Attenuates the PKA Signaling, Stress Response, and Virulence in the Human Opportunistic Pathogen Aspergillus fumigatus Lwin, Hnin Phyu Choi, Yong-Ho Lee, Min-Woo Yu, Jae-Hyuk Shin, Kwang-Soo Int J Mol Sci Article The regulator of G-protein signaling (RGS) proteins play an important role in upstream control of heterotrimeric G-protein signaling pathways. In the genome of the human opportunistic pathogenic fungus Aspergillus fumigatus, six RGS protein-encoding genes are present. To characterize the rgsA gene predicted to encode a protein with an RGS domain, we generated an rgsA null mutant and observed the phenotypes of the mutant. The deletion (Δ) of rgsA resulted in increased radial growth and enhanced asexual sporulation in both solid and liquid culture conditions. Accordingly, transcripts levels of the key asexual developmental regulators abaA, brlA, and wetA are elevated in the ΔrgsA mutant. Moreover, ΔrgsA resulted in elevated spore germination rates in the absence of a carbon source. The activity of cAMP-dependent protein kinase A (PKA) and mRNA levels of genes encoding PKA signaling elements are elevated by ΔrgsA. In addition, mRNA levels of genes associated with stress-response signaling increased with the lack of rgsA, and the ΔrgsA spores showed enhanced tolerance against oxidative stressors. Comparative transcriptomic analyses revealed that the ΔrgsA mutant showed higher mRNA levels of gliotoxin (GT) biosynthetic genes. Accordingly, the rgsA null mutant exhibited increased production of GT and elevated virulence in the mouse. Conversely, the majority of genes encoding glucan degrading enzymes were down-regulated by ΔrgsA, and endoglucanase activities were reduced. In summary, RgsA plays multiple roles, governing growth, development, stress responses, virulence, and external polymer degradation—likely by attenuating PKA signaling. MDPI 2019-11-11 /pmc/articles/PMC6888639/ /pubmed/31717953 http://dx.doi.org/10.3390/ijms20225628 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Lwin, Hnin Phyu
Choi, Yong-Ho
Lee, Min-Woo
Yu, Jae-Hyuk
Shin, Kwang-Soo
RgsA Attenuates the PKA Signaling, Stress Response, and Virulence in the Human Opportunistic Pathogen Aspergillus fumigatus
title RgsA Attenuates the PKA Signaling, Stress Response, and Virulence in the Human Opportunistic Pathogen Aspergillus fumigatus
title_full RgsA Attenuates the PKA Signaling, Stress Response, and Virulence in the Human Opportunistic Pathogen Aspergillus fumigatus
title_fullStr RgsA Attenuates the PKA Signaling, Stress Response, and Virulence in the Human Opportunistic Pathogen Aspergillus fumigatus
title_full_unstemmed RgsA Attenuates the PKA Signaling, Stress Response, and Virulence in the Human Opportunistic Pathogen Aspergillus fumigatus
title_short RgsA Attenuates the PKA Signaling, Stress Response, and Virulence in the Human Opportunistic Pathogen Aspergillus fumigatus
title_sort rgsa attenuates the pka signaling, stress response, and virulence in the human opportunistic pathogen aspergillus fumigatus
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6888639/
https://www.ncbi.nlm.nih.gov/pubmed/31717953
http://dx.doi.org/10.3390/ijms20225628
work_keys_str_mv AT lwinhninphyu rgsaattenuatesthepkasignalingstressresponseandvirulenceinthehumanopportunisticpathogenaspergillusfumigatus
AT choiyongho rgsaattenuatesthepkasignalingstressresponseandvirulenceinthehumanopportunisticpathogenaspergillusfumigatus
AT leeminwoo rgsaattenuatesthepkasignalingstressresponseandvirulenceinthehumanopportunisticpathogenaspergillusfumigatus
AT yujaehyuk rgsaattenuatesthepkasignalingstressresponseandvirulenceinthehumanopportunisticpathogenaspergillusfumigatus
AT shinkwangsoo rgsaattenuatesthepkasignalingstressresponseandvirulenceinthehumanopportunisticpathogenaspergillusfumigatus