Autoinducer 2 Signaling via the Phosphotransferase FruA Drives Galactose Utilization by <italic toggle="yes">Streptococcus pneumoniae</italic>, Resulting in Hypervirulence

ABSTRACT Communication between bacterial cells is crucial for the coordination of diverse cellular processes that facilitate environmental adaptation and, in the case of pathogenic species, virulence. This is achieved by the secretion and detection of small signaling molecules called autoinducers, a...

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Autores principales:	Claudia Trappetti, Lauren J. McAllister, Austen Chen, Hui Wang, Adrienne W. Paton, Marco R. Oggioni, Christopher A. McDevitt, James C. Paton
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/a35989f44ceb45f4b0c1ecfc45986c38
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spelling	oai:doaj.org-article:a35989f44ceb45f4b0c1ecfc45986c382021-11-15T15:51:06ZAutoinducer 2 Signaling via the Phosphotransferase FruA Drives Galactose Utilization by <italic toggle="yes">Streptococcus pneumoniae</italic>, Resulting in Hypervirulence10.1128/mBio.02269-162150-7511https://doaj.org/article/a35989f44ceb45f4b0c1ecfc45986c382017-03-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02269-16https://doaj.org/toc/2150-7511ABSTRACT Communication between bacterial cells is crucial for the coordination of diverse cellular processes that facilitate environmental adaptation and, in the case of pathogenic species, virulence. This is achieved by the secretion and detection of small signaling molecules called autoinducers, a process termed quorum sensing. To date, the only signaling molecule recognized by both Gram-positive and Gram-negative bacteria is autoinducer 2 (AI-2), synthesized by the metabolic enzyme LuxS (S-ribosylhomocysteine lyase) as a by-product of the activated methyl cycle. Homologues of LuxS are ubiquitous in bacteria, suggesting a key role in interspecies, as well as intraspecies, communication. Gram-negative bacteria sense and respond to AI-2 via the Lsr ABC transporter system or by the LuxP/LuxQ phosphorelay system. However, homologues of these systems are absent from Gram-positive bacteria and the AI-2 receptor is unknown. Here we show that in the major human pathogen Streptococcus pneumoniae, sensing of exogenous AI-2 is dependent on FruA, a fructose-specific phosphoenolpyruvate-phosphotransferase system that is highly conserved in Gram-positive pathogens. Importantly, AI-2 signaling via FruA enables the bacterium to utilize galactose as a carbon source and upregulates the Leloir pathway, thereby leading to increased production of capsular polysaccharide and a hypervirulent phenotype. IMPORTANCE S. pneumoniae is a Gram-positive bacterium frequently carried asymptomatically in the human nasopharynx. However, in a proportion of cases, it can spread to other sites of the body, causing life-threatening diseases that translate into massive global morbidity and mortality. Our data show that AI-2 signaling via FruA promotes the transition of the pneumococcus from colonization to invasion by facilitating the utilization of galactose, the principal sugar available in the upper respiratory tract. AI-2-mediated upregulation of Leloir pathway enzymes results in increased production of capsular polysaccharide and hypervirulence in a murine intranasal challenge model. This identifies the highly conserved FruA phosphotransferase system as a target for new antimicrobials based on the disruption of this generic quorum-sensing system.Claudia TrappettiLauren J. McAllisterAusten ChenHui WangAdrienne W. PatonMarco R. OggioniChristopher A. McDevittJames C. PatonAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 8, Iss 1 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Claudia Trappetti Lauren J. McAllister Austen Chen Hui Wang Adrienne W. Paton Marco R. Oggioni Christopher A. McDevitt James C. Paton Autoinducer 2 Signaling via the Phosphotransferase FruA Drives Galactose Utilization by <italic toggle="yes">Streptococcus pneumoniae</italic>, Resulting in Hypervirulence
description	ABSTRACT Communication between bacterial cells is crucial for the coordination of diverse cellular processes that facilitate environmental adaptation and, in the case of pathogenic species, virulence. This is achieved by the secretion and detection of small signaling molecules called autoinducers, a process termed quorum sensing. To date, the only signaling molecule recognized by both Gram-positive and Gram-negative bacteria is autoinducer 2 (AI-2), synthesized by the metabolic enzyme LuxS (S-ribosylhomocysteine lyase) as a by-product of the activated methyl cycle. Homologues of LuxS are ubiquitous in bacteria, suggesting a key role in interspecies, as well as intraspecies, communication. Gram-negative bacteria sense and respond to AI-2 via the Lsr ABC transporter system or by the LuxP/LuxQ phosphorelay system. However, homologues of these systems are absent from Gram-positive bacteria and the AI-2 receptor is unknown. Here we show that in the major human pathogen Streptococcus pneumoniae, sensing of exogenous AI-2 is dependent on FruA, a fructose-specific phosphoenolpyruvate-phosphotransferase system that is highly conserved in Gram-positive pathogens. Importantly, AI-2 signaling via FruA enables the bacterium to utilize galactose as a carbon source and upregulates the Leloir pathway, thereby leading to increased production of capsular polysaccharide and a hypervirulent phenotype. IMPORTANCE S. pneumoniae is a Gram-positive bacterium frequently carried asymptomatically in the human nasopharynx. However, in a proportion of cases, it can spread to other sites of the body, causing life-threatening diseases that translate into massive global morbidity and mortality. Our data show that AI-2 signaling via FruA promotes the transition of the pneumococcus from colonization to invasion by facilitating the utilization of galactose, the principal sugar available in the upper respiratory tract. AI-2-mediated upregulation of Leloir pathway enzymes results in increased production of capsular polysaccharide and hypervirulence in a murine intranasal challenge model. This identifies the highly conserved FruA phosphotransferase system as a target for new antimicrobials based on the disruption of this generic quorum-sensing system.
format	article
author	Claudia Trappetti Lauren J. McAllister Austen Chen Hui Wang Adrienne W. Paton Marco R. Oggioni Christopher A. McDevitt James C. Paton
author_facet	Claudia Trappetti Lauren J. McAllister Austen Chen Hui Wang Adrienne W. Paton Marco R. Oggioni Christopher A. McDevitt James C. Paton
author_sort	Claudia Trappetti
title	Autoinducer 2 Signaling via the Phosphotransferase FruA Drives Galactose Utilization by <italic toggle="yes">Streptococcus pneumoniae</italic>, Resulting in Hypervirulence
title_short	Autoinducer 2 Signaling via the Phosphotransferase FruA Drives Galactose Utilization by <italic toggle="yes">Streptococcus pneumoniae</italic>, Resulting in Hypervirulence
title_full	Autoinducer 2 Signaling via the Phosphotransferase FruA Drives Galactose Utilization by <italic toggle="yes">Streptococcus pneumoniae</italic>, Resulting in Hypervirulence
title_fullStr	Autoinducer 2 Signaling via the Phosphotransferase FruA Drives Galactose Utilization by <italic toggle="yes">Streptococcus pneumoniae</italic>, Resulting in Hypervirulence
title_full_unstemmed	Autoinducer 2 Signaling via the Phosphotransferase FruA Drives Galactose Utilization by <italic toggle="yes">Streptococcus pneumoniae</italic>, Resulting in Hypervirulence
title_sort	autoinducer 2 signaling via the phosphotransferase frua drives galactose utilization by <italic toggle="yes">streptococcus pneumoniae</italic>, resulting in hypervirulence
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/a35989f44ceb45f4b0c1ecfc45986c38
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Autoinducer 2 Signaling via the Phosphotransferase FruA Drives Galactose Utilization by <italic toggle="yes">Streptococcus pneumoniae</italic>, Resulting in Hypervirulence

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