Linked Life Data

17259175

Source:http://linkedlifedata.com/resource/pubmed/id/17259175

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
2007-4-2
pubmed:databankReference
pubmed:abstractText
Group B Streptococcus (GBS) frequently colonizes the human gastrointestinal and gynecological tracts and less frequently causes deep tissue infections. The transition between colonization and infection depends upon the ability of the organism to cross epithelial barriers. The alpha C protein (ACP) on the surface of GBS contributes to this process. A virulence factor in mouse models of infection, and prototype for a family of Gram-positive bacterial surface proteins, ACP facilitates GBS entry into human cervical epithelial cells and movement across cell layers. ACP binds to host cell surface glycosaminoglycan (GAG). From crystallography, we have identified a cluster of basic residues (BR2) that is a putative GAG binding area in Domain 2, near the junction of the N-terminal domain of ACP and the first of a series of tandem amino acid repeats. D2-R, a protein construct including this region, binds to cells similarly to full-length ACP. We now demonstrate that the predicted charged BR2 residues confer GAG binding; site-directed mutagenesis of these residues (Arg(172), Arg(185), or Lys(196)) eliminates cell-binding activity of construct D2-R. In addition, we have constructed a GBS strain expressing a variant ACP with a charge-neutralizing substitution at residue 185. This strain enters host cells less effectively than does the wild-type strain and similarly to an ACP null mutant strain. The point mutant strain transcytoses similarly to the wild-type strain. These data indicate that GAG-binding activity underlies ACP-mediated cellular entry of GBS. GBS entry into host cells and transcytosis of host cells may occur by distinct mechanisms.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
6
pubmed:volume
282
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
10526-36
pubmed:dateRevised
2008-10-20
pubmed:meshHeading
pubmed-meshheading:17259175-Amino Acid Sequence, pubmed-meshheading:17259175-Amino Acid Substitution, pubmed-meshheading:17259175-Animals, pubmed-meshheading:17259175-Antigens, Surface, pubmed-meshheading:17259175-Bacterial Adhesion, pubmed-meshheading:17259175-Bacterial Proteins, pubmed-meshheading:17259175-Bacterial Translocation, pubmed-meshheading:17259175-Binding Sites, pubmed-meshheading:17259175-Cell Line, Tumor, pubmed-meshheading:17259175-Cervix Uteri, pubmed-meshheading:17259175-Crystallography, X-Ray, pubmed-meshheading:17259175-Epithelial Cells, pubmed-meshheading:17259175-Female, pubmed-meshheading:17259175-Gastrointestinal Diseases, pubmed-meshheading:17259175-Genital Diseases, Female, pubmed-meshheading:17259175-Glycosaminoglycans, pubmed-meshheading:17259175-Humans, pubmed-meshheading:17259175-Mice, pubmed-meshheading:17259175-Molecular Sequence Data, pubmed-meshheading:17259175-Mutagenesis, Site-Directed, pubmed-meshheading:17259175-Point Mutation, pubmed-meshheading:17259175-Protein Binding, pubmed-meshheading:17259175-Protein Structure, Tertiary, pubmed-meshheading:17259175-Streptococcal Infections, pubmed-meshheading:17259175-Streptococcus agalactiae, pubmed-meshheading:17259175-Virulence Factors
pubmed:year
2007
pubmed:articleTitle
Identification of a glycosaminoglycan binding region of the alpha C protein that mediates entry of group B Streptococci into host cells.
pubmed:affiliation
Channing Laboratory, Department of Medicine, Brigham & Women's Hospital, Boston, Massachusetts 02115, USA. mbaron@partners.org
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural