title: The Haemophilus influenzae Hap serine protease promotes adherence and microcolony formation, potentiated by a soluble host protein.
abstract: Haemophilus influenzae initiates infection by colonizing the upper respiratory mucosa. The process of colonization involves adherence to epithelium and evasion of host immunity. In this study, we examined the H. influenzae Hap adhesin, which has serine protease activity and undergoes autoproteolytic cleavage and extracellular release in broth. We found that the uncleaved cell-associated form of Hap mediates adherence to cultured epithelial cells and promotes bacterial aggregation and microcolony formation. Adherence and aggregation are augmented by secretory leukocyte protease inhibitor, a natural component of respiratory secretions that inhibits Hap autoproteolysis. These observations suggest a novel paradigm in host-pathogen relations, in which a soluble host protein whose primary function is to protect host epithelium potentiates properties that facilitate bacterial colonization.
authors.affiliation: Edward Mallinckrodt Department of Pediatrics, Washington University School of Medicine, St. Louis Children's Hospital, Missouri 63110, USA.
authors.forename: D R
authors.initials: DR
authors.lastname: Hendrixson
authors.forename: J W
authors.initials: JW
authors.lastname: St Geme
mesh_terms: D001422:Bacterial Adhesion / Q000502:physiology*; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D001665:Binding Sites; D015169:Colony Count, Microbial; D006193:Haemophilus influenzae / Q000201:enzymology* / Q000254:growth & development / Q000472:pathogenicity; D006801:Humans; D006868:Hydrolysis; D008855:Microscopy, Electron, Scanning; D009154:Mutation; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins / Q000502:physiology*; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000382:microbiology
chemical_list: D001425:Bacterial Outer Membrane Proteins; C091552:Hap protein, Hemophilus influenzae; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D012697:Serine Endopeptidases