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)

New mutation detection systems are described for Haemophilus influenzae. They involve two independently isolated proline auxotrophs which appear to be mutants at different sites in a proline locus (proB) that is very closely linked to a locus (thd) for thymidine requirement. One of the mutants, proB1, appears to revert to prototrophy only by mutations at the locus. The other, proB2, reverts both by mutation at the locus and by unlinked suppressors. The latter account for about 90% of the reversions induced by MNNG and by HZ. The close linkage of proB to thd was used to distinguish between true revertants and suppressors by a transformation test. A comparison was made between the mutation induction kinetics of the different classes of revertants and mutations to novobiocin resistance with MNNG and HZ. The very different induction kinetics for these two mutagens previously reported for the novobiocin resistance system were also found for the proline systems. There were some differences between the detection systems, however, in the frequency of induced mutation relative to the spontaneous frequency and, in one case, in the form of the induction curve. It is concluded that the major features of the induction curves reflect the amount of damage done to DNA and so are general for all systems, but that there are some features which are locus-or site-specific.
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PMID:Reversions of two proline-requiring auxotrophs of Haemophilus influenzae by n-methyl-n'-nitro-n-nitrosoguanidine and hydrazine. 108 55

The alpha-aminoboronic acid analog of proline has been synthesized and incorporated into a number of peptides as the COOH-terminal residue. These peptide prolyl boronic acids are potent inhibitors of both the type 1 and type 2 IgA proteinases from Neisseria gonorrhoeae and Hemophilus influenzae, but not of the functionally similar IgA proteinase from Streptococcus sanguis. The best inhibitors synthesized thus far have Ki values in the nanomolar range (4.0 to 60 nM). These results indicate that the N. gonorrhoeae and the H. influenzae enzymes belong to the serine protease family of proteolytic enzymes while that from S. sanguis does not. As a group, the IgA proteinases have been noted for their remarkable specificity; thus, the peptide prolyl boronic acids reported here are the first small synthetic molecules to exhibit a relatively high affinity for the active site of an IgA proteinase and are therefore the first to yield some insight into the active site structure and specificity requirements of these enzymes.
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PMID:Inhibition of IgA1 proteinases from Neisseria gonorrhoeae and Hemophilus influenzae by peptide prolyl boronic acids. 210 53

Protease and peptidase enzymes are thought to play a role in the virulence of many oral organisms, especially those associated with periodontal diseases. In order to evaluate the peptidases of periodontopathogens, we compared the arylaminopeptidase activities of Bacteroides gingivalis with those of other oral and non-oral bacteria. Sixty-three bacterial strains representing the prominent cultivable organisms in human periodontal pockets were tested, including representatives of the black-pigmented Bacteroides, Actinobacillus, Actinomyces, Campylobacter, Capnocytophaga, Eikenella, Fusobacterium, Haemophilus, Lactobacillus, Streptococcus, and Veillonella species. Each micro-organism was examined for its ability to hydrolyze 18 synthetic substrates of beta-naphthylamide derivatives of amino acids, dipeptides, and tripeptides. Quantitation of the enzyme activity was accomplished by colorimetric measurement of the amounts of released beta-naphthylamines. N-CBz-glycyl-glycyl-L-arginine-beta-naphthylamide was readily cleaved by B. gingivalis, but slightly or not at all by the other oral strains tested. L-arginine-beta-naphthylamide was cleaved by B. gingivalis, Capnocytophaga species, and Streptococcus species, but not readily by the other Bacteroides strains. Some dipeptide substrates tested, such as glycyl-L-arginine- and glycyl-L-proline-beta-naphthylamide, were strongly cleaved by B. gingivalis and weakly cleaved by other Bacteroides strains. Since high levels of N-CBz-glycyl-glycyl-L-arginyl-aminopeptidase activity are characteristic of B. gingivalis, its measurement may be valuable in the identification of this organism in clinical samples as an aid in diagnosis and monitoring of periodontal infections. Furthermore, this and other aminopeptidases produced by B. gingivalis and other oral organisms may play a role in the tissue destruction seen in periodontal disease.
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PMID:Arylaminopeptidase activities of oral bacteria. 347 93

The major conclusion from these studies is that variants of Haemophilus influenzae Rd which restrict and modify phage S2 are metastable and capable of giving rise to one another with high frequency. Nonrestrictive RdS cells segregate spontaneously to the restricting, modifying phenotype in about 5% of the progeny of a single clone. The restrictive cells derived from RdS revert to the nonrestrictive phenotype in 15 to 25% of the progeny of a single clone. These frequencies are not appreciably affected by treatment with acriflavine or ethidium bromide, compounds which affect plasmid stability, or by nitrosoguanidine, a powerful mutagen. The genetic locus for restriction and modification of bacteriophage S2 is found to have a chromosomal position between the biotin and proline loci. Restriction-modification of phage S2 has been shown to be a function of its deoxyribonucleic acid (DNA) in that transfection with S2 phage DNA or prophage DNA is subject to host restriction and modification. An enzyme preparation, which contains endodeoxyribonuclease but no appreciable exonuclease activity, from mutant H. influenzae com(-10) did not restrict phage S2.RdS DNA or prophage DNA transfecting activity, indicating that this endodeoxyribonuclease is not responsible for phage restriction. A new restriction enzyme isolated from H. influenzae Rd was found to be the major enzyme involved in the restriction of bacteriophage S2. The enzyme inactivated the transfecting activity of unmodified phage DNA but did not attack modified phage DNA. Unlike endodeoxyribonuclease R, this enzyme requires adenosine triphosphate and S-adenosylmethionine.
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PMID:Restriction and modification of bacteriophage S2 in Haemophilus influenzae. 414 62

We report a 1.432-kb DNA sequence at 59 min on the Escherichia coli chromosome that connects the published sequences of the pcm gene for the isoaspartyl protein methyltransferase and that of the katF or rpoS (katF/rpoS) gene for a sigma factor involved in stationary-phase gene expression. Analysis of the DNA sequence reveals an open reading frame potentially encoding a polypeptide of 379 amino acids. The polypeptide sequence includes a consensus bacterial lipidation sequence present at residues 23 to 26 (Leu-Ala-Gly-Cys), four octapeptide proline- and glutamine-rich repeats of consensus sequence QQPQIQPV, and four heptapeptide threonine- and serine-rich repeats of consensus sequence PTA(S,T)TTE. The deduced amino acid sequence, especially in the C-terminal region, is similar to that of the Haemophilus somnus LppB lipoprotein outer membrane antigen (40% overall sequence identity; 77% identity in last 95 residues). The LppB lipoprotein binds Congo red dye and has been proposed to be a virulence determinant in H. somnus. Utilizing a plasmid construct with the E. coli gene under the control of a phage T7 promoter, we demonstrate the lipidation of this gene product by the incorporation of [3H]palmitic acid into a 42-kDa polypeptide. We also show that treatment of E. coli cells with globomycin, an inhibitor of the lipoprotein signal peptidase, results in the accumulation of a 46-kDa precursor. We thus designate the protein NlpD (new lipoprotein D). E. coli cells overexpressing NlpD bind Congo red dye, suggesting a common function with the H. somnus LppB protein. Disruption of the chromosomal E. coli nlpD gene by insertional mutagenesis results in decreased stationary-phase survival after 7 days.
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PMID:A gene at 59 minutes on the Escherichia coli chromosome encodes a lipoprotein with unusual amino acid repeat sequences. 813 57

Immunoglobulin A (IgA) proteases are bacterial enzymes with substrate specificity for human serum and secretory IgAs. To further define the basis of this specificity, we examined the ability of IgA proteases of Clostridium ramosum, Streptococcus pneumoniae (EC 3.4.24.13), Neisseria meningitidis (EC 3.4.21.72), and Haemophilus influenzae (EC 3.4.21.72) to cleave serum IgAs of gorillas, chimpanzees, and orangutans. All enzymes cleaved the IgAs of the three apes despite differences in ape IgA1 hinge sequence relative to the human prototype. To directly compare the ape and human hinge cleavage sites, the sites were identified in eight ape IgA digests. This analysis confirmed that ape proteins were all cleaved in the IgA hinge region, in all but one case after proline residues. The exception, C. ramosum protease, cleaved gorilla and chimpanzee IgAs at peptide bonds having no proline, but the scissile bonds were in the same hinge location as the Pro-221-Val-222 cleaved in human IgA1. These data indicate that proline is not an invariant substrate requirement for all IgA proteases and that the location of the scissile bond, in addition to its composition, is a critical determinant of cleavage specificity.
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PMID:Analysis of the specificity of bacterial immunoglobulin A (IgA) proteases by a comparative study of ape serum IgAs as substrates. 864 3

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

Corynebacterium glutamicum accumulates the compatible solutes proline, glycine betaine, and ectoine under conditions of high osmolality. Uptake of proline is mediated by both a high-affinity and a low-affinity secondary transport system. The low-affinity uptake system also accepts glycine betaine and ectoine as substrates. In the present study, the gene encoding the high-affinity proline uptake system PutP was isolated by heterologous complementation of Escherichia coli mutant strain WG389, which lacks the transport systems BetT, PutP, ProP, and ProU and is unable to synthesize proline and glycine betaine. This gene (putP) encodes a protein of 524 amino acids that shares identity with the proline transport systems PutP of E. coli, Staphylococcus aureus, Salmonella typhimurium, Haemophilus influenzae, and Klebsiella pneumoniae. Functional studies of PutP synthesized in E. coli mutant strain MKH13, which also lacks the transport systems for compatible solutes and is unable to synthesize glycine betaine, revealed that this carrier system is not regulated by the external osmolality on the level of activity. Km values of 7.6 mM for proline and 1.3 mM for sodium as cotransported ion were determined. Deletion of the putP gene allowed the functional characterization of another proline uptake system with low affinity.
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PMID:Isolation of the putP gene of Corynebacterium glutamicum and characterization of a low-affinity uptake system for compatible solutes. 923 6

Structural aspects of human TCRs that allow the activation of autoreactive T cells by diverse microbial peptides were examined using two human myelin basic protein (MBP)-specific T cell clones. The TCR sequences of these clones differed only in the N region of TCR-alpha and -beta since the clones had the same Valpha-Jalpha and Vbeta-Jbeta rearrangements. The two clones had a similar fine specificity for the MBP peptide, except for the P5 position of the peptide (lysine). In the crystal structure of the HLA-DR2/MBP peptide complex, P5 lysine is a prominent, solvent-exposed residue in the center of the DR2/MBP peptide surface. Five microbial peptides with conservative or nonconservative changes at the P5 position (lysine to arginine, serine, or proline) activated one of these clones. In contrast, the other clone was activated only by three of these peptides which had a conservative lysine to arginine change at P5. The degree of specificity/degeneracy in recognition of the P5 side chain was the key difference between these TCRs since the Escherichia coli/Haemophilus influenzae peptide stimulated both clones when the P5 position was substituted from serine to arginine. These results demonstrate that the complementarity-determining region 3 loops contribute to the degree of degeneracy in peptide recognition by human MBP-specific TCRs.
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PMID:Structural features of autoreactive TCR that determine the degree of degeneracy in peptide recognition. 988 4

Four Nudix hydrolase genes, ysa1 from Saccharomyces cerevisiae, orf209 from Escherichia coli, yqkg from Bacillus subtilis, and hi0398 from Hemophilus influenzae were amplified, cloned into an expression vector, and transformed into E. coli. The expressed proteins were purified and shown to belong to a subfamily of Nudix hydrolases active on ADP-ribose. Comparison with other members of the subfamily revealed a conserved proline 16 amino acid residues downstream of the Nudix box, common to all of the ADP-ribose pyrophosphatase subfamily. In this same region, a conserved tyrosine designates another subfamily, the diadenosine polyphosphate pyrophosphatases, while an array of eight conserved amino acids is indicative of the NADH pyrophosphatases. On the basis of these classifications, the trgB gene, a tellurite resistance factor from Rhodobacter sphaeroides, was predicted to designate an ADP-ribose pyrophosphatase. In support of this hypothesis, a highly specific ADP-ribose pyrophosphatase gene from the archaebacterium, Methanococcus jannaschii, introduced into E. coli, increased the transformant's tolerance to potassium tellurite.
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PMID:Studies on the ADP-ribose pyrophosphatase subfamily of the nudix hydrolases and tentative identification of trgB, a gene associated with tellurite resistance. 1054 72


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