Pneumococcal Metabolic Adaptation and Colonization Are Regulated by the Two-Component Regulatory System 08

ABSTRACT Streptococcus pneumoniae two-component regulatory systems (TCS) enable adaptation and ensure its maintenance in host environments. This study deciphers the impact of TCS08 on pneumococcal gene expression and its role in metabolic and pathophysiological processes. Transcriptome analysis and...

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Autores principales:	Alejandro Gómez-Mejia, Gustavo Gámez, Stephanie Hirschmann, Viktor Kluger, Hermann Rath, Sebastian Böhm, Franziska Voss, Niamatullah Kakar, Lothar Petruschka, Uwe Völker, Reinhold Brückner, Ulrike Mäder, Sven Hammerschmidt
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	Streptococcus pneumoniae colonization gene regulation physiology two-component regulatory systems Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/fabdf5b0b8c24203bfea2ceac3068e0b
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spelling	oai:doaj.org-article:fabdf5b0b8c24203bfea2ceac3068e0b2021-11-15T15:24:22ZPneumococcal Metabolic Adaptation and Colonization Are Regulated by the Two-Component Regulatory System 0810.1128/mSphere.00165-182379-5042https://doaj.org/article/fabdf5b0b8c24203bfea2ceac3068e0b2018-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSphere.00165-18https://doaj.org/toc/2379-5042ABSTRACT Streptococcus pneumoniae two-component regulatory systems (TCS) enable adaptation and ensure its maintenance in host environments. This study deciphers the impact of TCS08 on pneumococcal gene expression and its role in metabolic and pathophysiological processes. Transcriptome analysis and real-time PCR demonstrated a regulatory effect of TCS08 on genes involved mainly in environmental information processing, intermediary metabolism, and colonization by S. pneumoniae D39 and TIGR4. Striking examples are genes for fatty acid biosynthesis, genes of the arginine deiminase system, and the psa operon encoding the manganese ABC transport system. In silico analysis confirmed that TCS08 is homologous to Staphylococcus aureus SaeRS, and a SaeR-like binding motif is displayed in the promoter region of pavB, the upstream gene of the tcs08 operon encoding a surface-exposed adhesin. Indeed, PavB is regulated by TCS08 as confirmed by immunoblotting and surface abundance assays. Similarly, pilus-1 of TIGR4 is regulated by TCS08. Finally, in vivo infections using the acute pneumonia and sepsis models showed a strain-dependent effect. Loss of function of HK08 or TCS08 attenuated D39 virulence in lung infections. The RR08 deficiency attenuated TIGR4 in pneumonia, while there was no effect on sepsis. In contrast, lack of HK08 procured a highly virulent TIGR4 phenotype in both pneumonia and sepsis infections. Taken together, these data indicate the importance of TCS08 in pneumococcal fitness to adapt to the milieu of the respiratory tract during colonization. IMPORTANCE Streptococcus pneumoniae interplays with its environment by using 13 two-component regulatory systems and one orphan response regulator. These systems are involved in the sensing of environmental signals, thereby modulating pneumococcal pathophysiology. This study aimed to understand the functional role of genes subject to control by the TCS08. The identified genes play a role in transport of compounds such as sugars or amino acids. In addition, the intermediary metabolism and colonization factors are modulated by TCS08. Thus, TCS08 regulates genes involved in maintaining pneumococcal physiology, transport capacity, and adhesive factors to enable optimal colonization, which represents a prerequisite for invasive pneumococcal disease.Alejandro Gómez-MejiaGustavo GámezStephanie HirschmannViktor KlugerHermann RathSebastian BöhmFranziska VossNiamatullah KakarLothar PetruschkaUwe VölkerReinhold BrücknerUlrike MäderSven HammerschmidtAmerican Society for MicrobiologyarticleStreptococcus pneumoniaecolonizationgene regulationphysiologytwo-component regulatory systemsMicrobiologyQR1-502ENmSphere, Vol 3, Iss 3 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Streptococcus pneumoniae colonization gene regulation physiology two-component regulatory systems Microbiology QR1-502
spellingShingle	Streptococcus pneumoniae colonization gene regulation physiology two-component regulatory systems Microbiology QR1-502 Alejandro Gómez-Mejia Gustavo Gámez Stephanie Hirschmann Viktor Kluger Hermann Rath Sebastian Böhm Franziska Voss Niamatullah Kakar Lothar Petruschka Uwe Völker Reinhold Brückner Ulrike Mäder Sven Hammerschmidt Pneumococcal Metabolic Adaptation and Colonization Are Regulated by the Two-Component Regulatory System 08
description	ABSTRACT Streptococcus pneumoniae two-component regulatory systems (TCS) enable adaptation and ensure its maintenance in host environments. This study deciphers the impact of TCS08 on pneumococcal gene expression and its role in metabolic and pathophysiological processes. Transcriptome analysis and real-time PCR demonstrated a regulatory effect of TCS08 on genes involved mainly in environmental information processing, intermediary metabolism, and colonization by S. pneumoniae D39 and TIGR4. Striking examples are genes for fatty acid biosynthesis, genes of the arginine deiminase system, and the psa operon encoding the manganese ABC transport system. In silico analysis confirmed that TCS08 is homologous to Staphylococcus aureus SaeRS, and a SaeR-like binding motif is displayed in the promoter region of pavB, the upstream gene of the tcs08 operon encoding a surface-exposed adhesin. Indeed, PavB is regulated by TCS08 as confirmed by immunoblotting and surface abundance assays. Similarly, pilus-1 of TIGR4 is regulated by TCS08. Finally, in vivo infections using the acute pneumonia and sepsis models showed a strain-dependent effect. Loss of function of HK08 or TCS08 attenuated D39 virulence in lung infections. The RR08 deficiency attenuated TIGR4 in pneumonia, while there was no effect on sepsis. In contrast, lack of HK08 procured a highly virulent TIGR4 phenotype in both pneumonia and sepsis infections. Taken together, these data indicate the importance of TCS08 in pneumococcal fitness to adapt to the milieu of the respiratory tract during colonization. IMPORTANCE Streptococcus pneumoniae interplays with its environment by using 13 two-component regulatory systems and one orphan response regulator. These systems are involved in the sensing of environmental signals, thereby modulating pneumococcal pathophysiology. This study aimed to understand the functional role of genes subject to control by the TCS08. The identified genes play a role in transport of compounds such as sugars or amino acids. In addition, the intermediary metabolism and colonization factors are modulated by TCS08. Thus, TCS08 regulates genes involved in maintaining pneumococcal physiology, transport capacity, and adhesive factors to enable optimal colonization, which represents a prerequisite for invasive pneumococcal disease.
format	article
author	Alejandro Gómez-Mejia Gustavo Gámez Stephanie Hirschmann Viktor Kluger Hermann Rath Sebastian Böhm Franziska Voss Niamatullah Kakar Lothar Petruschka Uwe Völker Reinhold Brückner Ulrike Mäder Sven Hammerschmidt
author_facet	Alejandro Gómez-Mejia Gustavo Gámez Stephanie Hirschmann Viktor Kluger Hermann Rath Sebastian Böhm Franziska Voss Niamatullah Kakar Lothar Petruschka Uwe Völker Reinhold Brückner Ulrike Mäder Sven Hammerschmidt
author_sort	Alejandro Gómez-Mejia
title	Pneumococcal Metabolic Adaptation and Colonization Are Regulated by the Two-Component Regulatory System 08
title_short	Pneumococcal Metabolic Adaptation and Colonization Are Regulated by the Two-Component Regulatory System 08
title_full	Pneumococcal Metabolic Adaptation and Colonization Are Regulated by the Two-Component Regulatory System 08
title_fullStr	Pneumococcal Metabolic Adaptation and Colonization Are Regulated by the Two-Component Regulatory System 08
title_full_unstemmed	Pneumococcal Metabolic Adaptation and Colonization Are Regulated by the Two-Component Regulatory System 08
title_sort	pneumococcal metabolic adaptation and colonization are regulated by the two-component regulatory system 08
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/fabdf5b0b8c24203bfea2ceac3068e0b
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Pneumococcal Metabolic Adaptation and Colonization Are Regulated by the Two-Component Regulatory System 08

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