Neisseria meningitidis NhhA is a multifunctional trimeric autotransporter adhesin.
NhhA, Neisseriahia/hsf homologue, or GNA0992, is an oligomeric outer membrane protein of Neisseria meningitidis, recently included in the family of trimeric autotransporter adhesins. In this study we present the structural and functional characterization of this protein. By expressing in Escherichia coli the full-length gene, deletion mutants and chimeric proteins of NhhA, we demonstrated that the last 72 C-terminal residues are able to allow trimerization and localization of the N-terminal protein domain to the bacterial surface. In addition, we investigated on the possible role of NhhA in bacterial-host interaction events. We assessed in vitro the ability of recombinant purified NhhA to bind human epithelial cells as well as laminin and heparan sulphate. Furthermore, we shown that E. coli strain expressing NhhA was able to adhere to epithelial cells, and observed a reduced adherence in a meningococcal isogenic MC58DeltaNhhA mutant. We concluded that this protein is a multifunctional adhesin, able to promote the bacterial adhesion to host cells and extracellular matrix components. Collectively, our results underline a putative role of NhhA in meningococcal pathogenesis and ascertain its structural and functional belonging to the emerging group of bacterial autotransporter adhesins with trimeric architecture.
Scarselli
Maria
M
Novartis Vaccines, Via Fiorentina 1, 53100 Siena, Italy.
Serruto
Davide
D
Montanari
Paolo
P
Capecchi
Barbara
B
Adu-Bobie
Jeannette
J
Veggi
Daniele
D
Rappuoli
Rino
R
Pizza
Mariagrazia
M
Aricò
Beatrice
B
D018829:Adhesins, Bacterial / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D001422:Bacterial Adhesion; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000382:microbiology; D004926:Escherichia coli / Q000235:genetics / Q000502:physiology; D005109:Extracellular Matrix / Q000378:metabolism; D006497:Heparan Sulfate / Q000378:metabolism; D006801:Humans; D007797:Laminin / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D009345:Neisseria meningitidis / Q000502:physiology*; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D017386:Sequence Homology, Amino Acid
D018829:Adhesins, Bacterial; D002352:Carrier Proteins; D006497:Heparan Sulfate; D007797:Laminin