Protective activity of the CnaBE3 domain conserved among Staphylococcus aureus Sdr proteins.
Staphylococcus aureus is an opportunistic pathogen, commensal of the human skin and nares, but also responsible for invasive nosocomial as well as community acquired infections. Staphylococcus aureus adheres to the host tissues by means of surface adhesins, such as SdrC, SdrD, and SdrE proteins. The Sdr family of proteins together with a functional A domain, contain respectively two, three or five repeated sequences called B motifs which comprise the CnaB domains. SdrD and SdrE proteins were reported to be protective in animal models against invasive diseases or lethal challenge with human clinical S. aureus isolates. In this study we identified a 126 amino acid sequence containing a CnaB domain, conserved among the three Sdr proteins. The three fragments defined here as CnaBC2, D5 and E3 domains even though belonging to phylogenetically distinct strains, displayed high sequence similarity. Based on the sequence conservation data, we selected the CnaBE3 domain for further analysis and characterization. Polyclonal antibodies raised against the recombinant CnaBE3 domain recognized SdrE, SdrC and SdrD proteins of different S. aureus lineages. Moreover, we demonstrated that the CnaBE3 domain was expressed in vivo during S. aureus infections, and that immunization of this domain alone significantly reduces the bacterial load in mice challenged with S. aureus. Furthermore, we show that the reduction of bacteria by CnaBE3 vaccination is due to functional antibodies. Finally, we demonstrated that the region of the SdrE protein containing the CnaBE3 domain was resistant to trypsin digestion, a characteristic often associated with the presence of an isopeptide bond.
Novartis Vaccines and Diagnostics, Siena, Italy.
Marco
M
Becherelli
Prachi
P
Prachi
Elisa
E
Viciani
Massimiliano
M
Biagini
Luigi
L
Fiaschi
Emiliano
E
Chiarot
Sarah
S
Nosari
Cecilia
C
Brettoni
Sara
S
Marchi
Marco
M
Biancucci
Maria Rita
MR
Fontana
Francesca
F
Montagnani
Fabio
F
Bagnoli
Michèle A
MA
Barocchi
Andrea G O
AG
Manetti
D018829:Adhesins, Bacterial / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D000920:Antibody-Dependent Cell Cytotoxicity; D058491:Bacterial Load; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D017124:Conserved Sequence; D005260:Female; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010802:Phylogeny; D054730:Protein Interaction Domains and Motifs / Q000235:genetics / Q000276:immunology; D016415:Sequence Alignment; D013203:Staphylococcal Infections / Q000382:microbiology; D013211:Staphylococcus aureus / Q000145:classification / Q000235:genetics / Q000378:metabolism*
D018829:Adhesins, Bacterial; D000907:Antibodies, Bacterial; D001426:Bacterial Proteins