title: Identification and characterization of an antigen I/II family protein produced by group A Streptococcus.
abstract: Group A Streptococcus (GAS) is a gram-positive human bacterial pathogen that causes infections ranging in severity from pharyngitis to life-threatening invasive disease, such as necrotizing fasciitis. Serotype M28 strains are consistently isolated from invasive infections, particularly puerperal sepsis, a severe infection that occurs during or after childbirth. We recently sequenced the genome of a serotype M28 GAS strain and discovered a novel 37.4-kb foreign genetic element designated region of difference 2 (RD2). RD2 is similar in gene content and organization to genomic islands found in group B streptococci (GBS), the major cause of neonatal infections. RD2 encodes seven proteins with conventional gram-positive secretion signal sequences, six of which have not been characterized. Herein, we report that one of these six proteins (M28_Spy1325; Spy1325) is a member of the antigen I/II family of cell surface-anchored molecules produced by oral streptococci. PCR and DNA sequence analysis found that Spy1325 is very well conserved in GAS strains of distinct M protein serotypes. As assessed by real-time TaqMan quantitative PCR, the Spy1325 gene was expressed in vitro, and Spy1325 protein was present in culture supernatants and on the GAS cell surface. Western immunoblotting and enzyme-linked immunosorbent assays indicated that Spy1325 was produced by GAS in infected mice and humans. Importantly, the immunization of mice with recombinant Spy1325 fragments conferred protection against GAS-mediated mortality. Similar to other antigen I/II proteins, recombinant Spy1325 bound purified human salivary agglutinin glycoprotein. Spy1325 may represent a shared virulence factor among GAS, GBS, and oral streptococci.
authors.affiliation: Center for Molecular and Translational Human Infectious Diseases Research, The Methodist Hospital Research Institute, The Methodist Hospital, B154, 6565 Fannin St., Houston, TX 77030, USA.
authors.forename: Shizhen
authors.initials: S
authors.lastname: Zhang
authors.forename: Nicole M
authors.initials: NM
authors.lastname: Green
authors.forename: Izabela
authors.initials: I
authors.lastname: Sitkiewicz
authors.forename: Rance B
authors.initials: RB
authors.lastname: Lefebvre
authors.forename: James M
authors.initials: JM
authors.lastname: Musser
mesh_terms: D000483:Alleles; D000818:Animals; D000942:Antigens, Bacterial / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D001426:Bacterial Proteins / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D014644:Genetic Variation; D008297:Male; D051379:Mice; D013290:Streptococcal Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D022541:Streptococcal Vaccines / Q000235:genetics / Q000276:immunology; D013297:Streptococcus pyogenes / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D022223:Vaccines, Subunit / Q000235:genetics / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D022541:Streptococcal Vaccines; D022223:Vaccines, Subunit