Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/104105
Citations
Scopus Web of Science® Altmetric
?
?
Full metadata record
DC FieldValueLanguage
dc.contributor.authorTrappetti, C.en
dc.contributor.authorMcAllister, L.en
dc.contributor.authorChen, A.en
dc.contributor.authorWang, H.en
dc.contributor.authorPaton, A.en
dc.contributor.authorOggioni, M.en
dc.contributor.authorMcDevitt, C.en
dc.contributor.authorPaton, J.en
dc.date.issued2017en
dc.identifier.citationmBio, 2017; 8(1):e02269-16-1-e02269-16-18en
dc.identifier.issn2150-7511en
dc.identifier.issn2150-7511en
dc.identifier.urihttp://hdl.handle.net/2440/104105-
dc.description.abstractCommunication 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.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.en
dc.description.statementofresponsibilityClaudia Trappetti, Lauren J. McAllister, Austen Chen, Hui Wang, Adrienne W. Paton, Marco R. Oggioni, Christopher A. McDevitt, James C. Patonen
dc.language.isoenen
dc.publisherAmerican Society for Microbiologyen
dc.rightsCopyright © 2017 Trappetti et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.en
dc.subjectLung; Animals; Mice; Streptococcus pneumoniae; Pneumonia, Pneumococcal; Disease Models, Animal; Carbon; Lactones; Phosphoenolpyruvate Sugar Phosphotransferase System; Galactose; Bacterial Capsules; Homoserine; Histocytochemistry; Virulence; Signal Transduction; Gene Expression Regulation, Bacterialen
dc.titleAutoinducer 2 signaling via the phosphotransferase FruA drives galactose utilization by streptococcus pneumoniae, resulting in hypervirulenceen
dc.typeJournal articleen
dc.identifier.rmid0030063597en
dc.identifier.doi10.1128/mBio.02269-16en
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1071659en
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1080784en
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1043070en
dc.relation.granthttp://purl.org/au-research/grants/arc/DP150101856en
dc.relation.granthttp://purl.org/au-research/grants/arc/DE140100963en
dc.identifier.pubid284806-
pubs.library.collectionBiochemistry publicationsen
pubs.library.teamDS10en
pubs.verification-statusVerifieden
pubs.publication-statusPublisheden
dc.identifier.orcidTrappetti, C. [0000-0001-9807-5278]en
dc.identifier.orcidMcDevitt, C. [0000-0003-1596-4841]en
dc.identifier.orcidPaton, J. [0000-0001-8272-0068]en
Appears in Collections:Biochemistry publications

Files in This Item:
File Description SizeFormat 
hdl_104105.pdfPublished version3.33 MBAdobe PDFView/Open


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.