title: Group A streptococcus expresses a trio of surface proteins containing protective epitopes.
abstract: Group A streptococci (GAS) (Streptococcus pyogenes) are common causes of infections in humans for which there is no licensed vaccine. Decades of work has focused on the role of the surface M protein in eliciting type-specific protective immunity. Recent studies have identified additional surface proteins of GAS that contain opsonic epitopes. In the present study, we describe a serotype M65 GAS originally isolated during an epidemiologic study in Bamako, Mali, which simultaneously expressed M, M-related protein (Mrp), and streptococcal protective antigen (Spa) on the bacterial surface. The emm, mrp, and spa genes were sequenced from PCR amplicons derived from the M65 chromosome. Rabbit antisera raised against synthetic peptides copying the N-terminal regions of M, Mrp, and Spa were highly specific for each peptide, reacted with the surface of M65 GAS, and promoted bactericidal activity against the organism. A mixture of antisera against all three peptides was most effective in the bactericidal assays. Immunofluorescence microscopy revealed that the M, Mrp, and Spa antisera bound to the bacterial surface in the presence of human plasma proteins and resulted in the deposition of complement. Five additional spa genes were identified in the Mrp-positive GAS serotypes, and their sequences were determined. Our results indicate that there are multiple antigens on the surface of GAS that evoke antibodies that promote bacterial killing. A more complete understanding of the relative contributions of M, Mrp, and Spa in eliciting protective immunity may aid in the development of GAS vaccines with enhanced coverage and efficacy.
authors: Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA Department of Veterans Affairs Medical Center, Memphis, Tennessee, USA.
authors: Shannon E
authors: SE
authors: Niedermeyer
authors: Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA Department of Veterans Affairs Medical Center, Memphis, Tennessee, USA.
authors: Thomas A
authors: TA
authors: Penfound
authors: Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA Department of Veterans Affairs Medical Center, Memphis, Tennessee, USA.
authors: Claudia
authors: C
authors: Hohn
authors: Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA Department of Veterans Affairs Medical Center, Memphis, Tennessee, USA.
authors: Yi
authors: Y
authors: Li
authors: Bioinformatics Program, University of Memphis, Memphis, Tennessee, USA.
authors: Ramin
authors: R
authors: Homayouni
authors: Bioinformatics Program, University of Memphis, Memphis, Tennessee, USA.
authors: Jingnan
authors: J
authors: Zhao
authors: Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA Department of Microbiology, Immunology, and Biochemistry, University of Tennessee Health Science Center, Memphis, Tennessee, USA Department of Veterans Affairs Medical Center, Memphis, Tennessee, USA jbdale@uthsc.edu.
authors: James B
authors: JB
authors: Dale
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D000942:Antigens, Bacterial / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D001770:Blood Bactericidal Activity; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D003165:Complement System Proteins / Q000032:analysis; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D000939:Epitopes / Q000276:immunology*; D015870:Gene Expression; D006801:Humans; D008302:Mali; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D010802:Phylogeny; D011817:Rabbits; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D013297:Streptococcus pyogenes / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; D004269:DNA, Bacterial; D000939:Epitopes; D008565:Membrane Proteins; C105863:Mrp22 protein, Streptococcus; C014689:streptococcal M protein; C119204:streptococcal protective antigen; D003165:Complement System Proteins