Journal article
The classical lancefield antigen of group a Streptococcus is a virulence determinant with implications for vaccine design
Cell host & microbe, Vol.15(6), pp.729-740
06/11/2014
DOI: 10.1016/j.chom.2014.05.009
PMCID: PMC4078075
PMID: 24922575
Abstract
Group A Streptococcus (GAS) is a leading cause of infection-related mortality in humans. All GAS serotypes express the Lancefield group A carbohydrate (GAC), comprising a polyrhamnose backbone with an immunodominant N-acetylglucosamine (GlcNAc) side chain, which is the basis of rapid diagnostic tests. No biological function has been attributed to this conserved antigen. Here we identify and characterize the GAC biosynthesis genes, gacA through gacL. An isogenic mutant of the glycosyltransferase gacI, which is defective for GlcNAc side-chain addition, is attenuated for virulence in two infection models, in association with increased sensitivity to neutrophil killing, platelet-derived antimicrobials in serum, and the cathelicidin antimicrobial peptide LL-37. Antibodies to GAC lacking the GlcNAc side chain and containing only polyrhamnose promoted opsonophagocytic killing of multiple GAS serotypes and protected against systemic GAS challenge after passive immunization. Thus, the Lancefield antigen plays a functional role in GAS pathogenesis, and a deeper understanding of this unique polysaccharide has implications for vaccine development.
Details
- Title: Subtitle
- The classical lancefield antigen of group a Streptococcus is a virulence determinant with implications for vaccine design
- Creators
- Nina M van Sorge - Medical Microbiology, University Medical Center Utrecht,3584 CX Utrecht, The NetherlandsJason N Cole - Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, Queensland,QLD 4072, AustraliaKirsten Kuipers - Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, USAAnna Henningham - Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, USARamy K Aziz - Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University,11562 Cairo, EgyptAna Kasirer-Friede - Department of Medicine, University of California San Diego, La Jolla, CA 92093, USALeo Lin - Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, USAEvelien T M Berends - Medical Microbiology, University Medical Center Utrecht,3584 CX Utrecht, The NetherlandsMark R Davies - The Wellcome Trust Sanger Institute, The Wellcome Trust Genome Campus, Hinxton, CB10 1SA,United KingdomGordon Dougan - The Wellcome Trust Sanger Institute, The Wellcome Trust Genome Campus, Hinxton, CB10 1SA,United KingdomFan Zhang - Division of Infectious Diseases, Boston Children's Hospital, Boston, MA 02115, USASamira Dahesh - Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, USALaura Shaw - Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, USAJennifer Gin - Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA 92093, USAMadeleine Cunningham - Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USAJoseph A Merriman - Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USAJulia Hütter - Freie Universität Berlin, Institute of Chemistry and Biochemistry, Department of Biology, Chemistry and Pharmacy, 14195 Berlin, GermanyBernd Lepenies - Freie Universität Berlin, Institute of Chemistry and Biochemistry, Department of Biology, Chemistry and Pharmacy, 14195 Berlin, GermanySuzan H M Rooijakkers - Medical Microbiology, University Medical Center Utrecht,3584 CX Utrecht, The NetherlandsRichard Malley - Division of Infectious Diseases, Boston Children's Hospital, Boston, MA 02115, USAMark J Walker - Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, Queensland,QLD 4072, AustraliaSanford J Shattil - Department of Medicine, University of California San Diego, La Jolla, CA 92093, USAPatrick M Schlievert - Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USABiswa Choudhury - Glycobiology Research and Training Center, University of California San Diego, La Jolla, CA 92093, USAVictor Nizet - Glycobiology Research and Training Center, University of California San Diego, La Jolla, CA 92093, USA
- Resource Type
- Journal article
- Publication Details
- Cell host & microbe, Vol.15(6), pp.729-740
- Publisher
- United States
- DOI
- 10.1016/j.chom.2014.05.009
- PMID
- 24922575
- PMCID
- PMC4078075
- ISSN
- 1931-3128
- eISSN
- 1934-6069
- Grant note
- T32 GM007198 / NIGMS NIH HHS R01 AI077780 / NIAID NIH HHS R01 HL056595 / NHLBI NIH HHS HL5627 / NHLBI NIH HHS P01 HL107150 / NHLBI NIH HHS R01 AI052453 / NIAID NIH HHS U54 AI057153 / NIAID NIH HHS R01 AI096837 / NIAID NIH HHS HL35380 / NHLBI NIH HHS AI57153 / NIAID NIH HHS
- Language
- English
- Date published
- 06/11/2014
- Academic Unit
- Microbiology and Immunology; Internal Medicine
- Record Identifier
- 9984002396102771
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