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)

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

The composition of the peptidoglycan of Haemophilus influenzae was determined by analyzing glycopeptides generated by M1 muramidase hydrolysis using high pressure liquid chromatography, fast atom bombardment mass spectrometry, and fast atom bombardment collisionally activated dissociation tandem mass spectrometry, and amino acid analysis. The structures of 17 glycopeptides, representing 96% of the total peptidoglycan, were ascertained. Fifteen glycopeptides resembled species described for Escherichia coli peptidoglycan (Glauner, B., and Schwarz, U. (1983) The Target of Penicillin (Hackenbeck, R., ed), Walter de Gruyter, Berlin pp. 29-34) as compared with 9 in common with Bordetella pertussis (Tuomanen, E., Schwartz, J., Sande, S., Light, K., and Gage, D. (1989) J. Biol. Chem. 264, 11093-11098). Substitutions for L-alanine in the fourth position of the stem peptide included glycine, aspartic acid, and serine. The peptidoglycan was 27% cross-linked, 2% of which formed between diaminopimelic acid residues. No species was identified containing lysyl-arginine residues characteristic of lipoprotein. The peptidoglycan of non-beta-lactamase-mediated antibiotic-resistant H. influenzae differed from that of sensitive strains by an increase in the amount of disaccharide tripeptides and a decrease in 1,6-anhydro dimers. Both changes were transformable properties that changed in a stepwise fashion in parallel with the degree of antibiotic resistance.
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PMID:Composition of the peptidoglycan of Haemophilus influenzae. 850 90

Meropenem is a parenteral carbapenem antibiotic which has excellent bactericidal activity in vitro against almost all clinically significant aerobes and anaerobes. Its high activity is explained by ease of entry into bacteria combined with good affinity for essential penicillin binding proteins, including those associated with cell lysis. Breadth of spectrum is due, in part, to stability to all serine-based beta-lactamases, including those which hydrolyse third-generation cephalosporins. Meropenem has an antibacterial spectrum which is broadly similar to that of imipenem but, whilst slightly less active against staphylococci and enterococci, it is more active against Pseudomonas aeruginosa, all Enterobacteriaceae and Haemophilus influenzae. Amongst common human pathogens, only methicillin-resistant staphylococci and Enterococcus faecium are uniformly resistant to meropenem. The meropenem MICs for penicillin-resistant Streptococcus pneumoniae are higher than for penicillin-susceptible strains but the organisms remain susceptible. Clinical susceptibility in vitro to meropenem is defined by MICs of < or = 4 mg/L, intermediate susceptibility by MICs of 8 mg/L and MICs of > or = 16 mg/L define resistance; equivalent figures for zones of growth inhibition are > or = 14 (susceptible), 12-13 (intermediate) and < or = 11 (resistant) mm. Studies in guinea pig models of systemic infection and infections localised to the lungs, urinary tract and the central nervous system, some of which used immunocompromised animals, confirm the potential of meropenem demonstrated in vitro. These factors, combined with the human plasma, tissue or urinary concentrations of meropenem which exceed modal MICs for the pathogens isolated in clinical trials for most or all of the recommended 8 h dosing interval, predict that meropenem should be efficacious in the treatment of infections at many body sites.
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PMID:Meropenem: a microbiological overview. 854 86

Meropenem is a new carbapenem antibiotic that is stable to human renal dehydropeptidase-I (DHP-I) and exhibits potent bactericidal activity against almost all clinically significant aerobic and anaerobic bacteria. Activity is achieved through rapid entry into bacteria, resisting hydrolysis by all serine-based beta-lactamases, both of chromosomal or plasmid origin, and high affinity for vital penicillin binding proteins. The antibacterial spectrum of meropenem has been investigated extensively in a world-wide programme of studies. The results from all of these studies are consistent and identify in vitro differences between meropenem and imipenem. Both agents demonstrate high activity against Gram-positive aerobes with meropenem slightly less active than imipenem but significantly more potent than imipenem against Haemophilus influenza, all Enterobacteriaceae and 2-4 fold more active against Pseudomonas aeruginosa and most other pseudomonas. The spectrum of carbapenems is superior to that of all other beta-lactams. This is achieved, in part, by stability to the chromosomal beta-lactamases which hydrolyse ceftazidime, cefotaxime and ceftriaxone and against which newer agents like cefpirome and cefepime are not fully stable. Meropenem is also stable to the new plasmid-mediated enzymes which are responsible for significant elevation of MIC's of all cephalosporins and penicillins. When tested against P. Aeruginosa which have become resistant to imipenem therapy, these strains remained susceptible to meropenem. The activity of meropenem against anaerobes is at least as potent as metronidazole and clindamycin. These impressive in vitro data have been the basis for an extensive clinical evaluation programme in many indications including infections caused by single or multiple pathogens.
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PMID:[Preclinical evaluation of meropenem, a new parenteral carbapenem]. 857 29

The D-alanine:D-alanine-ligase-related enzymes can have three preferential substrate specificities. Usually, these enzymes synthesize D-alanyl-D-alanine. In vancomycin-resistant Gram-positive bacteria, structurally related enzymes synthesize D-alanyl-D-lactate or d-alanyl-d-serine. The sequence of internal fragments of eight structural d-alanine:d-alanine ligase genes from enterococci has been determined. Alignment of the deduced amino acid sequences with those of other related enzymes from Gram-negative and Gram-positive bacteria revealed the presence of four distinct sequence patterns in the putative substrate-binding sites, each correlating with specificity to a particular substrate (D-alanine:D-lactate ligases exhibited two patterns). Phylogenetic analysis showed different clusters. The enterococcal subtree was largely superimposable on that derived from 16S rRNA sequences. In lactic acid bacteria, structural divergence due to differences in substrate specificity was observed. Glycopeptide resistance proteins VanA and VanB, the VanC-type ligases, and DdlA and DdlB from enteric bacteria and Haemophilus influenzae constituted separate clusters.
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PMID:Evolution of structure and substrate specificity in D-alanine:D-alanine ligases and related enzymes. 866 22

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

The nucleotide sequences of the quinolone resistance-determining regions of the gyrA and parC genes from five ciprofloxacin-resistant strains of Haemophilus influenzae (MICs, 2 to 32 micrograms/ml) isolated from patients with cystic fibrosis and three ciprofloxacin-susceptible strains of H. influenzae (MICs, < or = 0.1 micrograms/ml) were determined. Four of the five resistant strains possessed at least one amino acid substitution in each of the GyrA and ParC fragments studied. The mutations identified in GyrA were a serine at residue 84 (Ser-84) to Leu or Tyr and Asp-88 to Asn or Tyr. ParC mutations were in positions exactly analogous to those identified in GyrA, namely, Ser-84 to Ile and Glu-88 to Lys. The Glu-88 to Lys ParC substitution was identified only in high-level ciprofloxacin-resistant strains. These mutations have been shown to be the origin of the observed resistance after transformation into ciprofloxacin-susceptible H. influenzae isolates. These results suggest that H. influenzae isolates require at least one amino acid substitution in both GyrA and ParC in order to attain significant levels of resistance to quinolones.
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PMID:Ciprofloxacin-resistant Haemophilus influenzae strains possess mutations in analogous positions of GyrA and ParC. 880 76

A novel thioredoxin-linked thiol peroxidase (Px) from Escherichia coli has been reported previously (M. K. Cha, H. K. Kim, and I. H. Kim, J. Biol. Chem. 270:28635-28641, 1995). In an attempt to perform physiological and biochemical characterizations of the thiol Px, a thiol Px null (tpx) mutant and a functional-residue mutant of thiol Px were produced. The tpx mutant was viable in aerobic culture but grew more slowly than the wild-type cells. The difference in growth rate became more pronounced when oxidative-stress-inducing reagents, such as peroxides and paraquat, were added to the cultures. The viability of the individual tpx mutant under oxidative stress was much lower than that of wild-type cells. tpx mutants growing aerobically respond to paraquat with a sixfold greater induction of Mn-superoxide dismutase than that of the wild-type cells. The deduced amino acid sequence of the thiol Px was found to be from 42 to 72% identical to the sequences of proteins from Haemophilus influenzae (ToxR regulon), Vibrio cholerae (ToxR regulon), and three kinds of streptococci (coaggregation-mediating adhesins), suggesting that they all belong to a new thiol Px family. Alignment of the amino acid sequences of the thiol Px family members showed that one cysteine, which corresponds to Cys-94 in E. coli thiol Px, is perfectly conserved. The substitution of serine for this cysteine residue resulted in complete loss of Px activity. These results suggest that the members of the thiol Px family, including E. coli thiol Px, have a functional cysteine residue and function in vivo as peroxidases.
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PMID:Mutation and Mutagenesis of thiol peroxidase of Escherichia coli and a new type of thiol peroxidase family. 882 4

The structural genes sdhA and sdhB, coding for the alpha- and beta-subunits of the [4Fe-4S] cluster containing L-serine dehydratase from Peptostreptococcus asaccharolyticus, have been cloned and sequenced. Expression of modified sdhB together with sdhA in Escherichia coli led to overproduction of active His6-tagged L-serine dehydratase. E. coli MEW22, deficient in the L-serine dehydratase L-SD1, was complemented by this sdhBA construct. The derived amino acid sequence of SdhBA shares similarities with both monomeric L-serine dehydratases, L-SD1 and L-SD2, from E. coli and with a putative L-serine dehydratase from Haemophilus influenzae, which suggests that these three enzymes are also iron-sulfur proteins.
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PMID:Cloning and expression of the two genes coding for L-serine dehydratase from Peptostreptococcus asaccharolyticus: relationship of the iron-sulfur protein to both L-serine dehydratases from Escherichia coli. 924 85

Whereas mammalian cells produce PS by a base exchange reaction from preexisting phospholipids, yeast cells synthesize PS from CDP-diacylglycerol and serine by the PS synthase reaction. Yeast PS synthase was purified to homogeneity and shown to have a molecular mass of 23 kDa. The activity is dependent on either Mg2+ or Mn2+ and Triton X-100. The enzyme specifically transfers the phosphatidyl group from CDP-diacylglycerol or dCDP-diacylglycerol to L-serine, but not to threonine, cysteine and ethanolamine. The PSS/CHO1 gene encoding the enzyme was cloned by the complementation of the choline auxotrophic pss/cho1 mutant. The deduced protein comprises 279 amino acids with a calculated molecular mass of 30,804. The primary translate undergoes proteolytic processing to the enzymatically more active 23-kDa enzyme. The deduced amino acid sequence contains several putative membrane-spanning regions and resembles that of the Bacillus subtilis enzyme, but not those of the E. coli and Haemophilus influenzae enzymes. The sequence also contains the local, conserved region found in enzymes catalyzing the transfer of the phosphoalcohol moiety from CDP-alcohol, such as PI synthase, cholinephosphotransferase and phosphatidylglycerolphosphate synthase. The activity of PS synthase is maximal in the exponential phase, but decreases when cells enter the stationary phase. The enzyme is phosphorylated at a single serine residue by cyclic AMP-dependent protein kinase with a 60-70% decrease in enzymatic activity, but the primary translation product is not phosphorylated. PS synthase is inhibited by CTP, probably due to the chelation of the divalent cations, Mg2+ and Mn2+, and also by sphingoid bases, such as sphinganine and phytosphingosine. Phosphatidate, phosphatidylcholine and phosphatidylinositol are stimulatory, whereas cardiolipin and diacylglycerol are inhibitory. The expression of yeast PS synthase is transcriptionally repressed by myo-inositol and choline in a coordinate manner with other phospholipid-synthesizing enzymes. The upstream regulatory region of the PSS/CHO1 gene responsible for the myo-inositol-choline regulation was identified. An octameric sequence, CATRTGAA (R = A or G), plays an important role in the conferral of the myo-inositol-choline transcriptional regulation.
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PMID:Phosphatidylserine synthase from yeast. 937 Mar 37


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