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Streptococcal Lance...
Streptococcal Lancefield polysaccharides are critical cell wall determinants for human Group IIA secreted phospholipase A2 to exert its bactericidal effects
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- van Hensbergen, Vincent P. (författare)
- Utrecht University,University Medical Center Utrecht
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- Movert, Elin (författare)
- Lund University,Lunds universitet,Infektionsimmunologi,Forskargrupper vid Lunds universitet,Infectious Immunology,Lund University Research Groups
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- de Maat, Vincent (författare)
- University Medical Center Utrecht,Utrecht University
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- Lüchtenborg, Christian (författare)
- Heidelberg University
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- Le Breton, Yoann (författare)
- University of Maryland
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- Lambeau, Gérard (författare)
- University of Côte d'Azur
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- Payré, Christine (författare)
- University of Côte d'Azur
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- Henningham, Anna (författare)
- University of California, San Diego
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- Nizet, Victor (författare)
- University of California, San Diego
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- van Strijp, Jos A.G. (författare)
- University Medical Center Utrecht,Utrecht University
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- Brügger, Britta (författare)
- Heidelberg University
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- Carlsson, Fredric (författare)
- Lund 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
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- McIver, Kevin S. (författare)
- University of Maryland
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- van Sorge, Nina M. (författare)
- University Medical Center Utrecht,Utrecht University
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(creator_code:org_t)
- 2018-10-15
- 2018
- Engelska.
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Ingår i: PLoS Pathogens. - : Public Library of Science (PLoS). - 1553-7374. ; 14:10, s. 1007348-1007348
- Relaterad länk:
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http://dx.doi.org/10... (free)
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https://journals.plo...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
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- Av författaren/redakt...
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van Hensbergen, ...
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Movert, Elin
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de Maat, Vincent
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Lüchtenborg, Chr ...
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Le Breton, Yoann
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Lambeau, Gérard
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visa fler...
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Payré, Christine
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Henningham, Anna
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Nizet, Victor
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van Strijp, Jos ...
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Brügger, Britta
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Carlsson, Fredri ...
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McIver, Kevin S.
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van Sorge, Nina ...
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visa färre...
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PLoS Pathogens
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Lunds universitet