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  • van Hensbergen, Vincent P.Utrecht University,University Medical Center Utrecht (författare)

Streptococcal Lancefield polysaccharides are critical cell wall determinants for human Group IIA secreted phospholipase A2 to exert its bactericidal effects

  • Artikel/kapitelEngelska2018

Förlag, utgivningsår, omfång ...

  • 2018-10-15
  • Public Library of Science (PLoS),2018

Nummerbeteckningar

  • LIBRIS-ID:oai:lup.lub.lu.se:2ce97b5b-e1dd-4f3a-b030-ea8de5e577c0
  • https://lup.lub.lu.se/record/2ce97b5b-e1dd-4f3a-b030-ea8de5e577c0URI
  • https://doi.org/10.1371/journal.ppat.1007348DOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:art swepub-publicationtype
  • Ämneskategori:ref swepub-contenttype

Anmärkningar

  • Human Group IIA secreted phospholipase A2 (hGIIA) is an acute phase protein with bactericidal activity against Gram-positive bacteria. Infection models in hGIIA transgenic mice have suggested the importance of hGIIA as an innate defense mechanism against the human pathogens Group A Streptococcus (GAS) and Group B Streptococcus (GBS). Compared to other Gram-positive bacteria, GAS is remarkably resistant to hGIIA activity. To identify GAS resistance mechanisms, we exposed a highly saturated GAS M1 transposon library to recombinant hGIIA and compared relative mutant abundance with library input through transposon-sequencing (Tn-seq). Based on transposon prevalence in the output library, we identified nine genes, including dltA and lytR, conferring increased hGIIA susceptibility. In addition, seven genes conferred increased hGIIA resistance, which included two genes, gacH and gacI that are located within the Group A Carbohydrate (GAC) gene cluster. Using GAS 5448 wild-type and the isogenic gacI mutant and gacI-complemented strains, we demonstrate that loss of the GAC N-acetylglucosamine (GlcNAc) side chain in the ΔgacI mutant increases hGIIA resistance approximately 10-fold, a phenotype that is conserved across different GAS serotypes. Increased resistance is associated with delayed penetration of hGIIA through the cell wall. Correspondingly, loss of the Lancefield Group B Carbohydrate (GBC) rendered GBS significantly more resistant to hGIIA-mediated killing. This suggests that the streptococcal Lancefield antigens, which are critical determinants for streptococcal physiology and virulence, are required for the bactericidal enzyme hGIIA to exert its bactericidal function.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Movert, ElinLund University,Lunds universitet,Infektionsimmunologi,Forskargrupper vid Lunds universitet,Infectious Immunology,Lund University Research Groups(Swepub:lu)med-emt (författare)
  • de Maat, VincentUniversity Medical Center Utrecht,Utrecht University (författare)
  • Lüchtenborg, ChristianHeidelberg University (författare)
  • Le Breton, YoannUniversity of Maryland (författare)
  • Lambeau, GérardUniversity of Côte d'Azur (författare)
  • Payré, ChristineUniversity of Côte d'Azur (författare)
  • Henningham, AnnaUniversity of California, San Diego (författare)
  • Nizet, VictorUniversity of California, San Diego (författare)
  • van Strijp, Jos A.G.University Medical Center Utrecht,Utrecht University (författare)
  • Brügger, BrittaHeidelberg University (författare)
  • Carlsson, FredricLund University,Lunds universitet,Infektionsimmunologi,Forskargrupper vid Lunds universitet,Molekylär cellbiologi,Biologiska institutionen,Naturvetenskapliga fakulteten,Infectious Immunology,Lund University Research Groups,Molecular Cell Biology,Department of Biology,Faculty of Science(Swepub:lu)mmb-fca (författare)
  • McIver, Kevin S.University of Maryland (författare)
  • van Sorge, Nina M.University Medical Center Utrecht,Utrecht University (författare)
  • Utrecht UniversityUniversity Medical Center Utrecht (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:PLoS Pathogens: Public Library of Science (PLoS)14:10, s. 1007348-10073481553-7374

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