Analysis of Two-Component Systems in Group B <italic toggle="yes">Streptococcus</italic> Shows That RgfAC and the Novel FspSR Modulate Virulence and Bacterial Fitness

ABSTRACT Group B Streptococcus (GBS), in the transition from commensal organisms to pathogens, will encounter diverse host environments and, thus, require coordinated control of the transcriptional responses to these changes. This work was aimed at better understanding the role of two-component sign...

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Autores principales:	Cristina Faralla, Matteo M. Metruccio, Matteo De Chiara, Rong Mu, Kathryn A. Patras, Alessandro Muzzi, Guido Grandi, Immaculada Margarit, Kelly S. Doran, Robert Janulczyk
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Lenguaje:	EN
Publicado:	American Society for Microbiology 2014
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/a8682af27e5a4646af6d0c0c7fdbb1cb
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spelling	oai:doaj.org-article:a8682af27e5a4646af6d0c0c7fdbb1cb2021-11-15T15:47:38ZAnalysis of Two-Component Systems in Group B <italic toggle="yes">Streptococcus</italic> Shows That RgfAC and the Novel FspSR Modulate Virulence and Bacterial Fitness10.1128/mBio.00870-142150-7511https://doaj.org/article/a8682af27e5a4646af6d0c0c7fdbb1cb2014-07-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00870-14https://doaj.org/toc/2150-7511ABSTRACT Group B Streptococcus (GBS), in the transition from commensal organisms to pathogens, will encounter diverse host environments and, thus, require coordinated control of the transcriptional responses to these changes. This work was aimed at better understanding the role of two-component signal transduction systems (TCS) in GBS pathophysiology through a systematic screening procedure. We first performed a complete inventory and sensory mechanism classification of all putative GBS TCS by genomic analysis. Five TCS were further investigated by the generation of knockout strains, and in vitro transcriptome analysis identified genes regulated by these systems, ranging from 0.1% to 3% of the genome. Interestingly, two sugar phosphotransferase systems appeared to be differentially regulated in the TCS-16 knockout strain (TCS loci were numbered in order of their appearance on the chromosome), suggesting an involvement in monitoring carbon source availability. High-throughput analysis of bacterial growth on different carbon sources showed that TCS-16 was necessary for the growth of GBS on fructose-6-phosphate. Additional transcriptional analysis provided further evidence for a stimulus-response circuit where extracellular fructose-6-phosphate leads to autoinduction of TCS-16, with concomitant dramatic upregulation of the adjacent operon, which encodes a phosphotransferase system. The TCS-16-deficient strain exhibited decreased persistence in a model of vaginal colonization. All mutant strains were also characterized in a murine model of systemic infection, and inactivation of TCS-17 (also known as RgfAC) resulted in hypervirulence. Our data suggest a role for the previously unknown TCS-16, here named FspSR, in bacterial fitness and carbon metabolism during host colonization, and the data also provide experimental evidence for TCS-17/RgfAC involvement in virulence. IMPORTANCE Two-component systems have been evolved by bacteria to detect environmental changes, and they play key roles in pathogenicity. A comprehensive analysis of TCS in GBS has not been performed previously. In this work, we classify 21 TCS and present evidence for the involvement of two specific TCS in GBS virulence and colonization in vivo. Although pinpointing specific TCS stimuli is notoriously difficult, we used a combination of techniques to identify two systems with different effects on GBS pathogenesis. For one of the systems, we propose that fructose-6-phosphate, a metabolite in glycolysis, is sufficient to induce a regulatory response involving a sugar transport system. Our catalogue and classification of TCS may guide further studies into the role of TCS in GBS pathogenicity and biology.Cristina FarallaMatteo M. MetruccioMatteo De ChiaraRong MuKathryn A. PatrasAlessandro MuzziGuido GrandiImmaculada MargaritKelly S. DoranRobert JanulczykAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 5, Iss 3 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Cristina Faralla Matteo M. Metruccio Matteo De Chiara Rong Mu Kathryn A. Patras Alessandro Muzzi Guido Grandi Immaculada Margarit Kelly S. Doran Robert Janulczyk Analysis of Two-Component Systems in Group B <italic toggle="yes">Streptococcus</italic> Shows That RgfAC and the Novel FspSR Modulate Virulence and Bacterial Fitness
description	ABSTRACT Group B Streptococcus (GBS), in the transition from commensal organisms to pathogens, will encounter diverse host environments and, thus, require coordinated control of the transcriptional responses to these changes. This work was aimed at better understanding the role of two-component signal transduction systems (TCS) in GBS pathophysiology through a systematic screening procedure. We first performed a complete inventory and sensory mechanism classification of all putative GBS TCS by genomic analysis. Five TCS were further investigated by the generation of knockout strains, and in vitro transcriptome analysis identified genes regulated by these systems, ranging from 0.1% to 3% of the genome. Interestingly, two sugar phosphotransferase systems appeared to be differentially regulated in the TCS-16 knockout strain (TCS loci were numbered in order of their appearance on the chromosome), suggesting an involvement in monitoring carbon source availability. High-throughput analysis of bacterial growth on different carbon sources showed that TCS-16 was necessary for the growth of GBS on fructose-6-phosphate. Additional transcriptional analysis provided further evidence for a stimulus-response circuit where extracellular fructose-6-phosphate leads to autoinduction of TCS-16, with concomitant dramatic upregulation of the adjacent operon, which encodes a phosphotransferase system. The TCS-16-deficient strain exhibited decreased persistence in a model of vaginal colonization. All mutant strains were also characterized in a murine model of systemic infection, and inactivation of TCS-17 (also known as RgfAC) resulted in hypervirulence. Our data suggest a role for the previously unknown TCS-16, here named FspSR, in bacterial fitness and carbon metabolism during host colonization, and the data also provide experimental evidence for TCS-17/RgfAC involvement in virulence. IMPORTANCE Two-component systems have been evolved by bacteria to detect environmental changes, and they play key roles in pathogenicity. A comprehensive analysis of TCS in GBS has not been performed previously. In this work, we classify 21 TCS and present evidence for the involvement of two specific TCS in GBS virulence and colonization in vivo. Although pinpointing specific TCS stimuli is notoriously difficult, we used a combination of techniques to identify two systems with different effects on GBS pathogenesis. For one of the systems, we propose that fructose-6-phosphate, a metabolite in glycolysis, is sufficient to induce a regulatory response involving a sugar transport system. Our catalogue and classification of TCS may guide further studies into the role of TCS in GBS pathogenicity and biology.
format	article
author	Cristina Faralla Matteo M. Metruccio Matteo De Chiara Rong Mu Kathryn A. Patras Alessandro Muzzi Guido Grandi Immaculada Margarit Kelly S. Doran Robert Janulczyk
author_facet	Cristina Faralla Matteo M. Metruccio Matteo De Chiara Rong Mu Kathryn A. Patras Alessandro Muzzi Guido Grandi Immaculada Margarit Kelly S. Doran Robert Janulczyk
author_sort	Cristina Faralla
title	Analysis of Two-Component Systems in Group B <italic toggle="yes">Streptococcus</italic> Shows That RgfAC and the Novel FspSR Modulate Virulence and Bacterial Fitness
title_short	Analysis of Two-Component Systems in Group B <italic toggle="yes">Streptococcus</italic> Shows That RgfAC and the Novel FspSR Modulate Virulence and Bacterial Fitness
title_full	Analysis of Two-Component Systems in Group B <italic toggle="yes">Streptococcus</italic> Shows That RgfAC and the Novel FspSR Modulate Virulence and Bacterial Fitness
title_fullStr	Analysis of Two-Component Systems in Group B <italic toggle="yes">Streptococcus</italic> Shows That RgfAC and the Novel FspSR Modulate Virulence and Bacterial Fitness
title_full_unstemmed	Analysis of Two-Component Systems in Group B <italic toggle="yes">Streptococcus</italic> Shows That RgfAC and the Novel FspSR Modulate Virulence and Bacterial Fitness
title_sort	analysis of two-component systems in group b <italic toggle="yes">streptococcus</italic> shows that rgfac and the novel fspsr modulate virulence and bacterial fitness
publisher	American Society for Microbiology
publishDate	2014
url	https://doaj.org/article/a8682af27e5a4646af6d0c0c7fdbb1cb
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Analysis of Two-Component Systems in Group B <italic toggle="yes">Streptococcus</italic> Shows That RgfAC and the Novel FspSR Modulate Virulence and Bacterial Fitness

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