Show simple item record

dc.contributor.authorTrappetti, C
dc.contributor.authorMcAllister, LJ
dc.contributor.authorChen, A
dc.contributor.authorWang, H
dc.contributor.authorPaton, AW
dc.contributor.authorOggioni, MR
dc.contributor.authorMcDevitt, CA
dc.contributor.authorPaton, JC
dc.date.accessioned2020-12-17T04:33:12Z
dc.date.available2020-12-17T04:33:12Z
dc.date.issued2017-01-01
dc.identifierpii: mBio.02269-16
dc.identifier.citationTrappetti, C., McAllister, L. J., Chen, A., Wang, H., Paton, A. W., Oggioni, M. R., McDevitt, C. A. & Paton, J. C. (2017). Autoinducer 2 Signaling via the Phosphotransferase FruA Drives Galactose Utilization by Streptococcus pneumoniae, Resulting in Hypervirulence. MBIO, 8 (1), https://doi.org/10.1128/mBio.02269-16.
dc.identifier.issn2150-7511
dc.identifier.urihttp://hdl.handle.net/11343/255358
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. 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.
dc.languageEnglish
dc.publisherAMER SOC MICROBIOLOGY
dc.titleAutoinducer 2 Signaling via the Phosphotransferase FruA Drives Galactose Utilization by Streptococcus pneumoniae, Resulting in Hypervirulence
dc.typeJournal Article
dc.identifier.doi10.1128/mBio.02269-16
melbourne.affiliation.departmentMicrobiology and Immunology
melbourne.source.titlemBio
melbourne.source.volume8
melbourne.source.issue1
melbourne.identifier.nhmrc1122582
dc.rights.licenseCC BY
melbourne.elementsid1337083
melbourne.contributor.authorMcDevitt, Christopher
dc.identifier.eissn2150-7511
melbourne.identifier.fundernameidNHMRC, 1122582
melbourne.accessrightsOpen Access


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record