title: Biological significance of IgA1 proteases in bacterial colonization and pathogenesis: critical evaluation of experimental evidence.
abstract: IgA1 protease activity, which allows bacteria to cleave human IgA1 in the hinge region, represents a striking example of convergent evolution of a specific property in bacteria. Although it has been known since 1979 that IgA1 protease is produced by the three leading causes of bacterial meningitis in addition to important urogenital pathogens and some members of the oropharyngeal flora, the exact role of this enzyme in bacterial pathogenesis is still incompletely understood owing to lack of a satisfactory animal model. Cleavage of IgA1 by these post-proline endopeptidases efficiently separates the monomeric antigen-binding fragments from the secondary effector functions of the IgA1 antibody molecule. Several in vivo and in vitro observations indicate that the enzymes are important for the ability of bacteria to colonize mucosal membranes in the presence of S-IgA antibodies. Furthermore, the extensive cleavage of IgA sometimes observed in vivo, suggests that IgA1 protease activity results in a local functional IgA deficiency that may facilitate colonization of other microorganisms and the penetration of potential allergens. It has been hypothesized that IgA1 protease activity of Haemophilus influenzae, Neisseria meningitidis, and Streptococcus pneumoniae, under special immunological circumstances, allows these bacteria to take advantage of specific IgA1 antibodies in a strategy to evade other immune factors of the human body. The decisive factor is the balance between IgA antibodies against surface antigens of the respective bacteria and their IgA1 protease. Recent studies have shown that serine-type IgA1 proteases of H. influenzae, meningococci, and gonococci belong to a family of proteins used by a diverse group of Gram-negative bacteria for colonization and invasion.
authors.affiliation: Department of Medical Microbiology and Immunology, Faculty of Health Sciences, University of Aarhus, Denmark.
authors.forename: M
authors.initials: M
authors.lastname: Kilian
authors.forename: J
authors.initials: J
authors.lastname: Reinholdt
authors.forename: H
authors.initials: H
authors.lastname: Lomholt
authors.forename: K
authors.initials: K
authors.lastname: Poulsen
authors.forename: E V
authors.initials: EV
authors.lastname: Frandsen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001419:Bacteria / Q000201:enzymology* / Q000276:immunology / Q000472:pathogenicity*; D001424:Bacterial Infections / Q000201:enzymology* / Q000276:immunology / Q000382:microbiology*; D006801:Humans; D007070:Immunoglobulin A / Q000502:physiology*; D008969:Molecular Sequence Data; D012697:Serine Endopeptidases / Q000502:physiology*; D014774:Virulence
chemical_list: D007070:Immunoglobulin A; D012697:Serine Endopeptidases; C021433:IgA-specific serine endopeptidase