title: PavB is a surface-exposed adhesin of Streptococcus pneumoniae contributing to nasopharyngeal colonization and airways infections.
abstract: The genomic analysis of Streptococcus pneumoniae strains identified the Pneumococcal adherence and virulence factor B (PavB), whose repetitive sequences, designated Streptococcal Surface REpeats (SSURE), interact with human fibronectin. Here, we showed the gene in all tested pneumococci and identified that the observed differences in the molecular mass of PavB rely on the number of repeats, ranging from five to nine SSURE. PavB interacted with fibronectin and plasminogen in a dose-dependent manner as shown by using various SSURE peptides. In addition, we identified PavB as colonization factor. Mice infected intranasally with DeltapavB pneumococci showed significantly increased survival times compared with wild-type bacteria. Importantly, the pavB-mutant showed a delay in transmigration to the lungs as observed in real-time using bioluminescent pneumococci and decreased colonization rates in a nasopharyngeal carriage model. In co-infection experiments the wild-type out-competed the pavB-mutant and infections of epithelial cells demonstrated that PavB contributes to adherence to host cell. Blocking experiments suggested a function of PavB as adhesin, which was confirmed by direct binding of SSURE peptides to host cells. Finally, PavB may represent a new vaccine candidate as SSURE peptides reacted with human sera. Taken together, PavB is a surface-exposed adhesin, which contributes to pneumococcal colonization and infections of the respiratory airways.
authors.affiliation: Department Genetics of Microorganisms, Institute for Genetics and Functional Genomics, University of Greifswald, D-17487 Greifswald, Germany.
authors.forename: Inga
authors.initials: I
authors.lastname: Jensch
authors.forename: Gustavo
authors.initials: G
authors.lastname: Gámez
authors.forename: Michael
authors.initials: M
authors.lastname: Rothe
authors.forename: Sandra
authors.initials: S
authors.lastname: Ebert
authors.forename: Marcus
authors.initials: M
authors.lastname: Fulde
authors.forename: Daniela
authors.initials: D
authors.lastname: Somplatzki
authors.forename: Simone
authors.initials: S
authors.lastname: Bergmann
authors.forename: Lothar
authors.initials: L
authors.lastname: Petruschka
authors.forename: Manfred
authors.initials: M
authors.lastname: Rohde
authors.forename: Roland
authors.initials: R
authors.lastname: Nau
authors.forename: Sven
authors.initials: S
authors.lastname: Hammerschmidt
mesh_terms: D018829:Adhesins, Bacterial / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001422:Bacterial Adhesion; D002353:Carrier State / Q000382:microbiology; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D004847:Epithelial Cells / Q000382:microbiology; D005260:Female; D005353:Fibronectins / Q000378:metabolism; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D008970:Molecular Weight; D009305:Nasopharynx / Q000382:microbiology*; D010958:Plasminogen / Q000378:metabolism; D011008:Pneumococcal Infections / Q000382:microbiology*; D011018:Pneumonia, Pneumococcal / Q000382:microbiology; D011485:Protein Binding; D020449:Repetitive Sequences, Amino Acid; D012137:Respiratory System / Q000382:microbiology*; D017422:Sequence Analysis, DNA; D013296:Streptococcus pneumoniae / Q000472:pathogenicity*; D016019:Survival Analysis; D037521:Virulence Factors / Q000737:chemistry / Q000235:genetics / Q000502:physiology*
chemical_list: D018829:Adhesins, Bacterial; D004269:DNA, Bacterial; D005353:Fibronectins; D037521:Virulence Factors; D010958:Plasminogen