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Cell Host Microbe. 2014 Jun 11;15(6):729-740. doi: 10.1016/j.chom.2014.05.009.

The classical lancefield antigen of group a Streptococcus is a virulence determinant with implications for vaccine design.

Author information

1
Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA.
2
Medical Microbiology, University Medical Center Utrecht,3584 CX Utrecht, The Netherlands.
3
Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, Queensland,QLD 4072, Australia.
4
Department of Bioengineering, University of California San Diego, La Jolla, CA 92093, USA.
5
Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University,11562 Cairo, Egypt.
6
Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
7
The Wellcome Trust Sanger Institute, The Wellcome Trust Genome Campus, Hinxton, CB10 1SA,United Kingdom.
8
Division of Infectious Diseases, Boston Children's Hospital, Boston, MA 02115, USA.
9
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA 92093, USA.
10
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City, OK 73104, USA.
11
Department of Microbiology, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA.
12
Max Planck Institute of Colloids and Interfaces, Department of Biomolecular Systems, 14476 Potsdam, Germany.
13
Freie Universität Berlin, Institute of Chemistry and Biochemistry, Department of Biology, Chemistry and Pharmacy, 14195 Berlin, Germany.
14
Glycobiology Research and Training Center, University of California San Diego, La Jolla, CA 92093, USA.
#
Contributed equally

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.

PMID:
24922575
PMCID:
PMC4078075
DOI:
10.1016/j.chom.2014.05.009
[Indexed for MEDLINE]
Free PMC Article

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