Postgenomic analysis of four novel antigens of group a streptococcus: growth phase-dependent gene transcription and human serologic response.
Analysis of three group A Streptococcus genomes (serotypes M1, M3, and M18) recently identified four previously undescribed genes that encode extracellular proteins. Each of these genes encode proteins with an LPXTG amino acid motif that covalently links many virulence factors produced by gram-positive bacteria to the cell surface. Western immunoblot analysis of serum samples obtained from 80 patients with invasive infections, noninvasive soft tissue infections, pharyngitis, and rheumatic fever indicated that these four proteins are expressed in vivo. However, the level of gene transcript and the time of maximal gene transcription varied in representative serotype M1, M3, and M18 strains. Surface expression of two proteins was confirmed by flow cytometry. Studies using a mouse infection model suggest that antibodies specific for one of the proteins (Spy0843) may contribute to a protective host immune response against a serotype M1 infection. These results are additional evidence that postgenomic strategies provide new ways to identify and investigate novel bacterial proteins that may participate in host-pathogen interactions or serve as targets for therapeutics research.
Reid
Sean D
SD
Laboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana 59840, USA.
Green
Nicole M
NM
Sylva
Gail L
GL
Voyich
Jovanka M
JM
Stenseth
Elisha T
ET
DeLeo
Frank R
FR
Palzkill
Timothy
T
Low
Donald E
DE
Hill
Harry R
HR
Musser
James M
JM
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015153:Blotting, Western; D005260:Female; D005434:Flow Cytometry; D016680:Genome, Bacterial; D006801:Humans; D007114:Immunization; D051379:Mice; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism; D012703:Serotyping; D013290:Streptococcal Infections / Q000276:immunology* / Q000382:microbiology / Q000517:prevention & control; D022541:Streptococcal Vaccines / Q000276:immunology; D013297:Streptococcus pyogenes / Q000235:genetics / Q000254:growth & development* / Q000276:immunology*; D014158:Transcription, Genetic
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D011994:Recombinant Proteins; D022541:Streptococcal Vaccines