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Query: UNIPROT:O75191 (H. influenzae)
 4,961 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immunoglobulin (Ig)A proteases synthesized by human mucosal pathogens have a unique specificity for human IgA and will not cleave IgA from other species. In contrast, animal pathogens have not reliably been shown to cleave IgA of the animals they infect. This lack of an animal model has prevented an understanding of the importance of IgA1 proteases as virulence factors. One strategy to develop an animal model would be to identify a species capable of infection by a human IgA-producing pathogen whose IgA was susceptible to cleavage by IgA1 protease of that bacterium. The chimpanzee can be infected with Haemophilus influenzae and is closely related immunologically to man. For these reasons it was sought to determine whether chimpanzee secretory IgA (SIgA) is susceptible to cleavage by IgA1 protease of H. influenzae. This report shows that chimpanzee SIgA can indeed be cleaved at the hinge region by H. influenzae IgA1 protease into Fab alpha and (Fc alpha)2.SC fragments. The susceptibility of chimpanzee SIgA to IgA1 protease of a human pathogen could serve as the basis of an animal model to determine the importance of IgA1 protease in pathogenesis.
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PMID:Cleavage of chimpanzee secretory immunoglobulin A by Haemophilus influenzae IgA1 protease. 179 27

Immunoglobulin A1 (IgA1) proteases are produced by a number of different species of bacteria which cause infection at human mucosal surfaces. The sole substrate of these proteases is human IgA1. Cleavage is within the hinge region of IgA1, although there is variability in the exact peptide bond within the hinge region that is cut by a particular protease. The cleavage site of the Haemophilus influenzae type 1 protease is located four amino acids from the cleavage site of the type 2 enzyme. In this study, the region of the H. influenzae IgA1 protease gene (iga) that determines the cleavage site specificity was localized through the comparison of the type 1 and type 2 genes and the construction and analysis of type 1-type 2 hybrid genes. The hybrid genes were generated by in vivo and in vitro techniques which facilitated the selection and screening of randomly generated hybrids. The cleavage site determinant was found to be within a 370-base-pair region near the amino-terminal coding region, in one of two large areas of nonhomology between the two types of H. influenzae iga genes. DNA sequence analysis of the cleavage site determinant and surrounding regions did not reveal a simple mechanism whereby one enzyme type could be converted to the other type. Comparison of the type 2 gonococcal IgA1 protease gene to the two Haemophilus genes revealed a significant amount of homology around the cleavage site determinant, with the two type 2 genes showing greater homology.
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PMID:Localization of the cleavage site specificity determinant of Haemophilus influenzae immunoglobulin A1 protease genes. 210 70

Indirect evidence suggests that immunoglobulin A1 (IgA1) proteases may be factors in the pathogenesis of certain infectious diseases, including meningitis, gonorrhoea, and destructive periodontitis. Bacterial IgA1 proteases are therefore potential candidates as vaccines. In this study, IgA1 proteases from 166 clinical isolates and reference strains of Haemophilus influenzae and Haemophilus aegyptius were compared with regard to specific activity and pattern of enzyme inhibition by antisera raised against IgA1 protease from nine selected strains of H. influenzae. A total of 93% of H. influenzae strains and all H. aegyptius strains had detectable IgA1 protease activity. The majority of strains cleaved a prolyl-seryl or a prolyl-threonyl peptide bond in the alpha 1 hinge region, whereas occasional H. influenzae strains possessed two separate IgA1 proteases with these two specific activities. Of the 155 IgA1 protease-producing strains, all except 12 could be assigned to one of 14 IgA1 protease "inhibition types," each defined by a characteristic pattern of inhibition by the nine antisera. There was no correlation between IgA1 protease type and biotype of the strains. However, among 92 encapsulated H. influenzae strains, a close correlation between capsular serotype and IgA1 protease type was observed. With the exception of serotype f, strains of all capsular serotypes produced an exclusive antigenic type of IgA1 protease. All 38 strains of serotype b produced IgA1 protease of inhibition type 1, which was never demonstrated in non-encapsulated H. influenzae strains. These results facilitate the detection of an antibody response against specific IgA1 proteases and are of practical value for a possible future vaccine against H. influenzae serotype b infections.
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PMID:Antigenic heterogeneity of immunoglobulin A1 proteases from encapsulated and non-encapsulated Haemophilus influenzae. 619 13

Haemophilus influenzae is one of several bacterial pathogens known to release IgA1 proteases into the extracellular environment. Each H. influenzae isolate produces one of at least three distinct types of these enzymes that differ in the specific peptide bond they cleave in the hinge region of human IgA1. We have isolated the gene specifying type 1 IgA1 protease from a total genomic library of H. influenzae, subcloned it into plasmid vectors, and introduced these vectors into Escherichia coli K-12. The enzyme synthesized by E. coli was active and had the same specificity as that of the H. influenzae donor. Unlike that of the donor, E. coli protease activity accumulated in the periplasm rather than being transported extracellularly. The position of the protease gene in H. influenzae DNA and its direction of transcription was approximated by deletion mapping. Tn5 insertions, and examination of the polypeptides synthesized by minicells. A 1-kilobase probe excised from the IgA1 protease gene hybridized with DNA restriction fragments of all H. influenzae serogroups but not with DNA of a nonpathogenic H. parainfluenzae species known to be IgA1 protease negative.
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PMID:IgA1 proteases of Haemophilus influenzae: cloning and characterization in Escherichia coli K-12. 634 96

IgA1 proteases of two distinct specificities were demonstrated among 95 isolates of Haemophilus influenzae and nine isolates of H. aegyptius. The two enzymes cleaved two different peptide bonds in the hinge region of the alpha chain of IgA1: a prolyl-seryl bond located at position 231-232 (type A cleavage) and a prolyl-threonyl peptide bond between residues 235 and 236 (type B cleavage). Each strain of H. influenzae produced either one or both of these types of enzymes, whereas all H. aegyptius strains produced type A enzyme only. The application of enzyme-neutralizing antibodies to the study of IgA1 proteases produced by the 104 strains of H. influenzae and H. aegyptius revealed at least 15 different types of protease activities based on inhibition patterns in nine selected antibody preparations. The types of IgA1 proteases closely correlated with the serotype of encapsulated strains of H. influenzae. The study suggests that H. influenzae strains produce at least two serologically different IgA1 proteases with distinct or identical enzymatic activities.
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PMID:Molecular biology of Haemophilus influenzae IgA1 proteases. 635 64

IgA1 proteases from H. influenzae, N. meningitidis, S. pneumoniae, and S. sanguis were compared with respect to site of cleavage in the IgA1 molecule and EDTA sensitivity. Proteases from S. sanguis and S. pneumoniae cleaved the Pro (227)-Thr (228) bond within the hinge region of the alpha 1 chain and were inhibited by EDTA. H. influenzae IgA1 protease cleaved the Pro (231)-Ser (232) peptide bond. The activity of IgA1 proteases from H. influenzae and N. meningitidis was unaffected by EDTA. Purified and denatured alpha 1 chain was cleaved only in the hinge region. Other component chains of secretory IgA (secretory component, light and J chains) were not susceptible. In addition to IgA1 protease, S. pneumoniae released exo- and endoglycosidases that removed a considerable portion of carbohydrate side chains of IgA1; this activity was absent from crude IgA1 protease preparations of the other three bacterial species. Association in vitro of polymeric IgA1 with SC did not inhibit the degradation of IgA1 proteases. The considerable resistance of secretory IgA to cleavage by IgA1 proteases may be explained in part by the presence of IgA1 protease-neutralizing antibodies in secretory IgA.
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PMID:IgA1 proteases from Haemophilus influenzae, Streptococcus pneumoniae, Neisseria meningitidis, and Streptococcus sanguis: comparative immunochemical studies. 676 97

Haemophilus influenzae is one of five bacterial species known to produce IgA proteases, enzymes that specifically cleave the human IgA1 heavy chain. Strains of H. influenzae produce three distinct types of IgA proteases that cleave different peptide bonds within the IgA1 hinge region. Type 1 protease cleaves the prolyl-seryl bond at position 231-232; type 2 protease cleaves the prolyl-threonyl bond at position 235-236, the same bond attacked by Neisseria gonorrhoeae and Neisseria meningitidis type 2 proteases. Type 3 protease yields a unique double Fd cleavage pattern; the exact peptide bonds cleaved have not been determined. The type of protease produced correlates with the serotype, but not with the biotype, of the isolate; serotypes A, B, D, and F produce primarily type 1 protease, whereas serotypes C and E produce only type 2 enzyme. Each nontypable strain yields one of the three protease types. These data further extend our knowledge of the extreme specificity of the IgA proteases and suggest that IgA protease type may be useful in the taxonomy and epidemiology of H. influenzae.
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PMID:Relationship between the specificity of IgA proteases and serotypes in Haemophilus influenzae. 680 43

Bacterial pathogens of the genera Neisseria and Haemophilus secrete IgA1 proteinases which cleave human IgA1 in the heavy chain hinge region. The exact peptide bond cleaved is strain-dependent, but remains invariant despite repeated subculture. Haemophilus influenzae and Neisseria meningitidis produce proteinases of two cleavage site specificities (type 1 and type 2). We examined serial acute and convalescent sera from patients recovering from meningitis due to N. meningitidis or H. influenzae, and found a significant rise in serum titer of inhibitory antibodies against these enzymes. In each case the proteinase from the infecting organism was more susceptible to inhibition than were proteinases from that genus that had different cleavage specificity. Inhibition of sixteen type 1-type 2 hybrid H. influenzae IgA1 proteinases revealed complete concordance between inhibitory titer and cleavage site specificity. Inhibition of hybrid proteinases differing in a 123 amino acid segment known to determine cleavage site specificity (termed the CSD) further localized the site of antibody action to this site. These results from a limited number of patients with natural infections suggest that inhibiting antibody recognizes epitopes within the CSD. Alternatively, antibody may bind to epitopes outside the CSD and inhibit via steric hindrance.
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PMID:Post-infectious human serum antibodies inhibit IgA1 proteinases by interaction with the cleavage site specificity determinant. 841 25

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.
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PMID:Biological significance of IgA1 proteases in bacterial colonization and pathogenesis: critical evaluation of experimental evidence. 870 38

Immunoglobulin A1 (IgA1) proteases cleaving human IgA1 in the hinge region are produced constitutively by a number of pathogens, including Haemophilus influenzae, Neisseria meningitidis, Neisseria gonorrhoeae, and Streptococcus pneumoniae, as well as by some members of the resident oropharyngeal flora. Whereas IgA1 proteases have been shown to interfere with the functions of IgA antibodies in vitro, the exact role of these enzymes in the relationship of bacteria to a human host capable of responding with enzyme-neutralizing antibodies is not clear. Conceivably, the role of IgA1 proteases may depend on the quantity of IgA1 protease generated as well as on the balance between secreted and cell-associated forms of the enzyme. Therefore, we have compared levels of IgA1 protease activity in cultures of 38 bacterial strains representing different genera and species as well as strains of different pathogenic potential. Wide variation in activity generation rate was found overall and within some species. High activity was not an exclusive property of bacteria with documented pathogenicity. Almost all activity of H. influenzae, N. meningitidis, and N. gonorrhoeae strains was present in the supernatant. In contrast, large proportions of the activity in Streptococcus, Prevotella, and Capnocytophaga species was cell associated at early stationary phase, suggesting that the enzyme may play the role of a surface antigen. Partial release of cell-associated activity occurred during stationary phase. Within some taxa, the degree of activity variation correlated with degree of antigenic diversity of the enzyme as determined previously. This finding may indicate that the variation observed is of biological significance.
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PMID:Comparative analysis of immunoglobulin A1 protease activity among bacteria representing different genera, species, and strains. 935 19


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