Two-Component Signaling Regulates Osmotic Stress Adaptation via SskA and the High-Osmolarity Glycerol MAPK Pathway in the Human Pathogen <italic toggle="yes">Talaromyces marneffei</italic>

ABSTRACT For successful infection to occur, a pathogen must be able to evade or tolerate the host’s defense systems. This requires the pathogen to first recognize the host environment and then signal this response to elicit a complex adaptive program in order to activate its own defense strategies....

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Autores principales:	Kylie J. Boyce, Cunwei Cao, Alex Andrianopoulos
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2016
Materias:	Two-component signaling dimorphism morphogenesis pathogenicity response regulator Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/34d90f58bc9544a7b6257f04c0182953
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spelling	oai:doaj.org-article:34d90f58bc9544a7b6257f04c01829532021-11-15T15:21:39ZTwo-Component Signaling Regulates Osmotic Stress Adaptation via SskA and the High-Osmolarity Glycerol MAPK Pathway in the Human Pathogen <italic toggle="yes">Talaromyces marneffei</italic>10.1128/mSphere.00086-152379-5042https://doaj.org/article/34d90f58bc9544a7b6257f04c01829532016-02-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00086-15https://doaj.org/toc/2379-5042ABSTRACT For successful infection to occur, a pathogen must be able to evade or tolerate the host’s defense systems. This requires the pathogen to first recognize the host environment and then signal this response to elicit a complex adaptive program in order to activate its own defense strategies. In both prokaryotes and eukaryotes, two-component signaling systems are utilized to sense and respond to changes in the external environment. The hybrid histidine kinases (HHKs) at the start of the two-component signaling pathway have been well characterized in human pathogens. However, how these HHKs regulate processes downstream currently remains unclear. This study describes the role of a response regulator downstream of these HHKs, sskA, in Talaromyces marneffei, a dimorphic human pathogen. sskA is required for asexual reproduction, hyphal morphogenesis, cell wall integrity, osmotic adaptation, and the morphogenesis of yeast cells both in vitro at 37°C and during macrophage infection, but not during dimorphic switching. Comparison of the ΔsskA mutant with a strain in which the mitogen-activated protein kinase (MAPK) of the high-osmolarity glycerol pathway (SakA) has been deleted suggests that SskA acts upstream of this pathway in T. marneffei to regulate these morphogenetic processes. This was confirmed by assessing the amount of phosphorylated SakA in the ΔsskA mutant, antifungal resistance due to a lack of SakA activation, and the ability of a constitutively active sakA allele (sakAF316L) to suppress the ΔsskA mutant phenotypes. We conclude that SskA regulates morphogenesis and osmotic stress adaptation in T. marneffei via phosphorylation of the SakA MAPK of the high-osmolarity glycerol pathway. IMPORTANCE This is the first study in a dimorphic fungal pathogen to investigate the role of a response regulator downstream of two-component signaling systems and its connection to the high-osmolarity glycerol pathway. This study will inspire further research into the downstream components of two-component signaling systems and their role during pathogenic growth.Kylie J. BoyceCunwei CaoAlex AndrianopoulosAmerican Society for MicrobiologyarticleTwo-component signalingdimorphismmorphogenesispathogenicityresponse regulatorMicrobiologyQR1-502ENmSphere, Vol 1, Iss 1 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Two-component signaling dimorphism morphogenesis pathogenicity response regulator Microbiology QR1-502
spellingShingle	Two-component signaling dimorphism morphogenesis pathogenicity response regulator Microbiology QR1-502 Kylie J. Boyce Cunwei Cao Alex Andrianopoulos Two-Component Signaling Regulates Osmotic Stress Adaptation via SskA and the High-Osmolarity Glycerol MAPK Pathway in the Human Pathogen <italic toggle="yes">Talaromyces marneffei</italic>
description	ABSTRACT For successful infection to occur, a pathogen must be able to evade or tolerate the host’s defense systems. This requires the pathogen to first recognize the host environment and then signal this response to elicit a complex adaptive program in order to activate its own defense strategies. In both prokaryotes and eukaryotes, two-component signaling systems are utilized to sense and respond to changes in the external environment. The hybrid histidine kinases (HHKs) at the start of the two-component signaling pathway have been well characterized in human pathogens. However, how these HHKs regulate processes downstream currently remains unclear. This study describes the role of a response regulator downstream of these HHKs, sskA, in Talaromyces marneffei, a dimorphic human pathogen. sskA is required for asexual reproduction, hyphal morphogenesis, cell wall integrity, osmotic adaptation, and the morphogenesis of yeast cells both in vitro at 37°C and during macrophage infection, but not during dimorphic switching. Comparison of the ΔsskA mutant with a strain in which the mitogen-activated protein kinase (MAPK) of the high-osmolarity glycerol pathway (SakA) has been deleted suggests that SskA acts upstream of this pathway in T. marneffei to regulate these morphogenetic processes. This was confirmed by assessing the amount of phosphorylated SakA in the ΔsskA mutant, antifungal resistance due to a lack of SakA activation, and the ability of a constitutively active sakA allele (sakAF316L) to suppress the ΔsskA mutant phenotypes. We conclude that SskA regulates morphogenesis and osmotic stress adaptation in T. marneffei via phosphorylation of the SakA MAPK of the high-osmolarity glycerol pathway. IMPORTANCE This is the first study in a dimorphic fungal pathogen to investigate the role of a response regulator downstream of two-component signaling systems and its connection to the high-osmolarity glycerol pathway. This study will inspire further research into the downstream components of two-component signaling systems and their role during pathogenic growth.
format	article
author	Kylie J. Boyce Cunwei Cao Alex Andrianopoulos
author_facet	Kylie J. Boyce Cunwei Cao Alex Andrianopoulos
author_sort	Kylie J. Boyce
title	Two-Component Signaling Regulates Osmotic Stress Adaptation via SskA and the High-Osmolarity Glycerol MAPK Pathway in the Human Pathogen <italic toggle="yes">Talaromyces marneffei</italic>
title_short	Two-Component Signaling Regulates Osmotic Stress Adaptation via SskA and the High-Osmolarity Glycerol MAPK Pathway in the Human Pathogen <italic toggle="yes">Talaromyces marneffei</italic>
title_full	Two-Component Signaling Regulates Osmotic Stress Adaptation via SskA and the High-Osmolarity Glycerol MAPK Pathway in the Human Pathogen <italic toggle="yes">Talaromyces marneffei</italic>
title_fullStr	Two-Component Signaling Regulates Osmotic Stress Adaptation via SskA and the High-Osmolarity Glycerol MAPK Pathway in the Human Pathogen <italic toggle="yes">Talaromyces marneffei</italic>
title_full_unstemmed	Two-Component Signaling Regulates Osmotic Stress Adaptation via SskA and the High-Osmolarity Glycerol MAPK Pathway in the Human Pathogen <italic toggle="yes">Talaromyces marneffei</italic>
title_sort	two-component signaling regulates osmotic stress adaptation via sska and the high-osmolarity glycerol mapk pathway in the human pathogen <italic toggle="yes">talaromyces marneffei</italic>
publisher	American Society for Microbiology
publishDate	2016
url	https://doaj.org/article/34d90f58bc9544a7b6257f04c0182953
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Two-Component Signaling Regulates Osmotic Stress Adaptation via SskA and the High-Osmolarity Glycerol MAPK Pathway in the Human Pathogen <italic toggle="yes">Talaromyces marneffei</italic>

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