Structural and Functional Analysis of Cell Wall-anchored Polypeptide Adhesin BspA in Streptococcus agalactiae.
Streptococcus agalactiae (group B Streptococcus, GBS) is the predominant cause of early-onset infectious disease in neonates and is responsible for life-threatening infections in elderly and immunocompromised individuals. Clinical manifestations of GBS infection include sepsis, pneumonia, and meningitis. Here, we describe BspA, a deviant antigen I/II family polypeptide that confers adhesive properties linked to pathogenesis in GBS. Heterologous expression of BspA on the surface of the non-adherent bacterium Lactococcus lactis confers adherence to scavenger receptor gp340, human vaginal epithelium, and to the fungus Candida albicans Complementary crystallographic and biophysical characterization of BspA reveal a novel β-sandwich adhesion domain and unique asparagine-dependent super-helical stalk. Collectively, these findings establish a new bacterial adhesin structure that has in effect been hijacked by a pathogenic Streptococcus species to provide competitive advantage in human mucosal infections.
From the School of Oral and Dental Sciences, University of Bristol, Bristol BS1 2LY, United Kingdom, the School of Biochemistry, University of Bristol, Bristol BS8 1TD, United Kingdom.
Sara
S
Rego
the School of Biochemistry, University of Bristol, Bristol BS8 1TD, United Kingdom, the Bristol Centre for Functional Nanomaterials, University of Bristol, Bristol BS8 1TL, United Kingdom.
Timothy J
TJ
Heal
From the School of Oral and Dental Sciences, University of Bristol, Bristol BS1 2LY, United Kingdom.
Grace R
GR
Pidwill
the School of Biochemistry, University of Bristol, Bristol BS8 1TD, United Kingdom, the BrisSynBio Synthetic Biology Research Centre, University of Bristol, Bristol BS8 1TQ, United Kingdom, and.
Marisa
M
Till
the School of Biochemistry, University of Bristol, Bristol BS8 1TD, United Kingdom.
Alice
A
Robson
the Department of Oral Immunology and Infectious Diseases, University of Louisville, Louisville, Kentucky 40202.
Richard J
RJ
Lamont
the School of Biochemistry, University of Bristol, Bristol BS8 1TD, United Kingdom, the BrisSynBio Synthetic Biology Research Centre, University of Bristol, Bristol BS8 1TQ, United Kingdom, and.
Richard B
RB
Sessions
From the School of Oral and Dental Sciences, University of Bristol, Bristol BS1 2LY, United Kingdom.
Howard F
HF
Jenkinson
the School of Biochemistry, University of Bristol, Bristol BS8 1TD, United Kingdom, the BrisSynBio Synthetic Biology Research Centre, University of Bristol, Bristol BS8 1TQ, United Kingdom, and paul.race@bristol.ac.uk.
Paul R
PR
Race
From the School of Oral and Dental Sciences, University of Bristol, Bristol BS1 2LY, United Kingdom, angela.nobbs@bristol.ac.uk.
Angela H
AH
Nobbs
D018829:Adhesins, Bacterial / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D001422:Bacterial Adhesion / Q000502:physiology; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002176:Candida albicans / Q000235:genetics / Q000378:metabolism; D002473:Cell Wall / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D013294:Lactococcus lactis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D000072417:Protein Domains; D017433:Protein Structure, Secondary; D013292:Streptococcus agalactiae / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship
D018829:Adhesins, Bacterial; D001426:Bacterial Proteins; C105995:BspA protein, bacteria; D008565:Membrane Proteins
AgI/II family polypeptide; Candida albicans; Streptococcus; adhesin; bacterial adhesion; bacterial pathogenesis; protein conformation; structural model; structure-function; x-ray crystallography