Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0348321 (Haemophilus)
 15,372 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The amino acid sequence T-P-P-T-P-S-P-S is tandemly duplicated in the heavy chain of human immunoglobulin A1 (IgA1), the major antibody in secretions. The bacterial pathogen Streptococcus sanguis, a precursor to dental caries and a cause of bacterial endocarditis, yields IgA protease that cleaves only the Pro-Thr peptide bond in the left duplication, while the type 2 IgA proteases of the genital pathogen Neisseria gonorrhoeae and the respiratory pathogen Haemophilus influenzae cleave only the P-T bond in the right half. We have sequenced the entire S. sanguis iga gene cloned into Escherichia coli. A segment consisting of 20 amino acids tandemly repeated 10 times, of unknown function, occurs near the amino-terminal end of the enzyme encoded in E. coli. Identification of a predicted zinc-binding region in the S. sanguis enzyme and the demonstration that mutations in this region result in production of a catalytically inactive protein support the idea that the enzyme is a metalloprotease. The N. gonorrhoeae and H. influenzae enzymes were earlier shown to be serine-type proteases, while the Bacteroides melaninogenicus IgA protease was shown to be a cysteine-type enzyme. The streptococcal IgA protease amino acid sequence has no significant homology with either of the two previously determined IgA protease sequences, that of type 2 N. gonorrhoeae and type 1 H. influenzae. The differences in both structure and mechanism among these functionally analogous enzymes underscore their role in the infectious process and offer some prospect of therapeutic intervention.
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PMID:Analysis of the immunoglobulin A protease gene of Streptococcus sanguis. 198 65

Fibronectinolytic activity from two Gram-positive microorganisms (Streptococcus mutans and Bacterionema matruchotii), and from three Gram-negative oral bacteria (Bacteroides intermedius, Bacteroides gingivalis and Haemophilus actinomycetemcomitans) were compared. 125I-labelled human plasma fibronectin (FN) was incubated either either with bacterial extracts or with concentrated culture medium samples and the patterns of FN-degradation products were determined by SDS-PAGE. Results to date have shown that Streptococcus mutans, Bacterionema matruchotii and Haemophilus actinomycetemcomitans were unable to degrade FN. On the other hand the Gram-negative Bacteroides intermedius and Bacteroides gingivalis were shown to contain Fn-degrading activity. The highest activity was found in the bacterial extracts of Bacteroides gingivalis. Inhibition assays demonstrated that fibronectinolytic activity of Bacteroides gingivalis occurred predominantly by cysteine proteinase(s) while that of Bacteroides intermedius by a common action of serine and cysteine proteinases.
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PMID:A comparison of fibronectinolytic activities from several oral bacteria. 269 52

Human neutrophils contain large amounts of a neutral serine protease, human neutrophil elastase (HNE), which has been implicated as a mediator of acute and chronic lung injury. We found that this enzyme is effectively inhibited, at physiological ionic strength, by several synthetic non-base-paired polyribonucleotides. Among the most active of these is polyguanylic acid (poly G). Inhibitory activity is greatest with high-molecular-weight poly G fractions, but poly G fractions even as low as 60K Mr (app) are effective. Both amidolysis of synthetic elastase substrates, such as succinyl-ala-ala-ala-p-nitroanilide, and proteolysis of elastin are blocked. Poly G inhibits elastin proteolysis even when subsequently added to mixtures of elastin and HNE that have first been preincubated together for 10 min. Under these conditions, polyribosylribitol phosphate, a polyanion derived from Haemophilus influenzae capsular polysaccharide, is not inhibitory. Complex formation between HNE and poly G is dependent on ionic rather than covalent interactions, since it is blocked by 0.6 M NaCl but not by inactivation of the enzyme's catalytic-site serine residue with diisopropylfluorophosphate. However, nonspecific ionic interactions alone cannot explain complex formation, since pancreatic elastase and cathepsin G, an even more basic serine protease from human neutrophils, do not form complexes with poly G, even at low ionic strength. Moreover, in the presence of the amphiphiles taurocholic acid and glycocholic acid, HNE is much less effectively blocked by poly G. Peptide chloromethyl ketone-inactivate HNE (which has its extended substrate-binding pocket occupied by the peptidyl inactivator) also fails to form complexes with poly G. These results indicate that HNE may utilize both hydrophobic and ionic binding sites to couple with poly G, and suggest that these sites may be close to or within the extended substrate-binding pocket of the enzyme.
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PMID:Inhibition of human neutrophil elastase by polyguanylic acid and other synthetic RNA homopolymers. 325 33

Resistance of bacteria to beta-lactam antibiotics has become a serious problem in the past several decades. Virtually all Staphylococcus aureus, and many Hemophilus influenzae, Branhamella catarrhalis, Neisseria gonorrhoeae, Enterobacteriaceae, and Bacteroides species possess beta-lactamases that hydrolyze penicillins and cephalosporins. The most common plasmid-mediated beta-lactamase is the TEM enzyme (Richmond-Sykes type IIIa), which is present in Hemophilus, Neisseria, and Enterobacteriaceae. One technique to overcome bacterial resistance has been the development of beta-lactamase inhibitors. Clavulanic acid is a beta-lactamase inhibitor that inhibits the beta-lactamases of S. aureus, Hemophilus, Neisseria, Branhamella, Eschericia coli, Klebsiella, and Bacteroides. Clavulanate acts as a "suicide" inhibitor, forming a stable enzyme complex that binds to serine at the active site of the enzyme. Clavulanate readily crosses the outer cell wall of most Enterobacteriaceae to interact with beta-lactamases in the periplasmic space. Clavulanate does not inhibit beta-lactamases such as the Richmond-Sykes type I enzymes found in Pseudomonas aeruginosa, Enterobacter, and Citrobacter species, which are inducible enzymes that function primarily as cephalosporinases.
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PMID:Contribution of beta-lactamases to bacterial resistance and mechanisms to inhibit beta-lactamases. 390 41

Nutritional mutants of Haemophilus influenzae requiring l-serine for growth were shown to be deficient in their capacity to synthesize serine-phosphate from 3-phosphoglycerate. On the basis of the correlation between this block and the requirement for an exogenous supply of the amino acid, it was concluded that the "phosphorylated" pathway is the only pathway used by H. influenzae for serine biosynthesis. Serine inhibits serine-phosphate production, thereby regulating its own synthesis in a manner analagous to the Enterobacteriaceae. A mutant strain that required either serine or tryptophan for growth was normal in serine-phosphate synthesis and regulation. It was concluded that this strain probably has a tryptophan synthetase with an increased Michaelis constant for serine.
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PMID:Serine biosynthesis and regulation in Haemophilus influenzae. 530 3

Employing a combination of chemical and spectroscopic techniques, the structure of the Haemophilus influenzae type d capsular polysaccharide was found to be leads to 4)-beta-D-GlcNAc-(1 leads to 3)-beta-D-ManNAcA-(1 leads to. L-Alanine, L-serine, and L-threonine, in the molar ratios of approximately 1.0:1.0:0.3, were linked to C-6 of the D-mannosyluronic residue as amides; the (serine + alanine + threonine) to ManNAcA ratio was approximately 0.95:1.0. Removal of the amino acids by mild hydrolysis with sodium hydroxide resulted in a material that was cross-reactive with the native, type d polymer. The base-treated, type d polysaccharide was not observed to cross-react with either the H. influenzae type e or Escherichia coli K7 capsular polysaccharide, both of which are structurally similar to type d.
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PMID:Structural and immunological studies of the Haemophilus influenzae type d capsular polysaccharide. 679 29

The structure of the capsular polysaccharide elaborated by Haemophilus influenzae type d has been investigated, methylation analysis and n.m.r. spectrometry being the principal methods used. It is concluded that the polysaccharide is composed of repeating units having the structure: leads to 4)-beta-D-GlcpNAc-(1 leads to 3)-beta-D-ManpNAcA-(1 leads to. In addition, single residues of L-alanine, L-serine, or L-threonine, in the proportions 2:2:1, are linked, through their amino groups, to C-6 of the 2-acetamido-2-deoxy-beta-D-mannopyranosyluronic acid residues. The degree of substitution (75-85%) varies for different preparations.
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PMID:Structural studies of the capsular polysaccharide elaborated by Haemophilus influenza type d. 697 5

The immune response to the P6 protein of Haemophilus influenzae was characterized with 24 synthetic icosapeptides and 45 dodecapeptides conjugated to the immune stimulator N-palmitoyl-S-[2,3-(bispalmitoyloxy)-(2RS)-propyl]-(R)-cysteinyl-( S)-serine . The antigenicity of these lipopeptides was investigated by enzyme-linked immunosorbent assays with rabbit anti-P6 serum. The epitopes of P6 protein were identified and localized within residues 31-46 and 59-70 and in the C-terminal part of the P6 protein. Mice were immunized with lipoicosapeptides without using additional adjuvants or carriers and the antibody titers were measured with isolated P6 protein and lipopeptides in a dot blot assay. Lipopeptides containing the sequence pattern QILDAHAA (P6 47-54) and the mouse B cell epitope GEYV (P6 43-46) induced high titers of anti P6 antibodies. These murine antibodies were able to neutralize the intact bacterium Haemophilus influenzae.
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PMID:Mapping of antigenic and immunogenic sites of Haemophilus influenzae outer membrane protein P6 using synthetic lipopeptides. 751 62

Haemophilus influenzae represents a common cause of human disease and an important source of morbidity and mortality. Disease caused by this organism begins with colonization of the upper respiratory tract. Several studies indicate that H. influenzae is capable of binding to and entering cultured human cells, properties which are potentially of relevance to the process of colonization. In the present study, we isolated an H. influenzae gene designated hap, which is associated with the capacity for in vitro attachment and entry. Analysis of the derived amino acid sequence of hap demonstrated significant homology with the serine-type IgA1 proteases expressed by H. influenzae and Neisseria gonorrhoeae. It is notable that the hap product shares the catalytic domain of the IgA1 proteases and appears to be processed and secreted in an analogous manner. We speculate that the hap gene product is an important determinant of colonization, perhaps enabling the organism to evade the local immune response and thereby persist within the respiratory tract.
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PMID:A Haemophilus influenzae IgA protease-like protein promotes intimate interaction with human epithelial cells. 783 May 68

To investigate the antigenic variation and relationships of immunoglobulin A1 (IgA1) proteases among different species and genera, we examined a comprehensive collection of serine type and metallo-type IgA1 proteases and corresponding antisera in enzyme neutralization assays. Sharing of neutralizing epitopes of metallo-type IgA1 proteases from Streptococcus pneumoniae, Streptococcus sanguis, Streptococcus mitis, and Streptococcus oralis and of serine type IgA1 proteases from Haemophilus and pathogenic Neisseria species was extremely limited. A number of limited to strong cross-reactions in such epitopes were found among serine type IgA1 proteases released by members of the genera Haemophilus and Neisseria, reflecting the common origin of their iga gene. However, the relatively limited prevalence of shared "neutralizing" epitopes of IgA1 proteases from the two genera indicates that they rarely induce immunity to each other. In contrast, extensive sharing of neutralizing epitopes was found between N. meningitidis and N. gonorrhoeae IgA1 proteases, making them potentially attractive vaccine components. Among metallo-type IgA1 proteases, several pneumococcal proteases were found to induce neutralizing antibodies to IgA1 proteases of oral streptococci whereas the opposite was not the case.
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PMID:Antigenic relationships among immunoglobulin A1 proteases from Haemophilus, Neisseria, and Streptococcus species. 803 86


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