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)

In three male patients with lower respiratory disease, aged 51, 32 and 63 years, Legionnaires' disease was diagnosed by urinary antigen test and culture of the respiratory-tract fluid. In the second patient, the bronchoalveolar fluid also contained Streptococcus pneumoniae and Haemophilus influenzae. All three patients recovered after treatment with azithromycin in the first, cefotaxime, vancomycin and levofloxacin in the second, and erythromycin and ciprofloxacin in the third, respectively. Legionella pneumophila pneumonia is clinically not clearly distinct from other pneumonias and has a high mortality rate when not treated with the proper antibiotics. For that reason, adequate and swift diagnosis is of great importance. The urinary antigen test meets both of these criteria. Still, it is advisable to use culture and serology as well if Legionnaires' disease is suspected in a patient, since the urinary antigen test has limitations. In addition, patient isolates are ofepidemiological importance for public health. By comparing available patient isolates with Legionella strains from water sources, it is possible to identify sources of infection. In 2002, based on this principle, a project was started in The Netherlands aimed at identifying sources of infection, thereby preventing outbreaks of Legionnaires' disease by swift elimination of the source. Since the start of the project, 29 sources have been identified. In the cases described above these were a sauna, a cooling tower and a caravan, respectively. In suspected cases, respiratory-tract fluid must be collected to make possible such a source investigation.
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PMID:[Three patients with pneumonia due to Legionella associated with a sauna, a cooling tower and a caravan in The Netherlands]. 1617 Nov 14

Most heterosexual women want to reduce the risk of acquiring a sexually transmitted infection; many also want to control their fertility. Several chemical agents have been proposed to dramatically slow the spread of HIV infections. Ideally, vaginal microbicides, with or without contraceptive properties, should be safe, effective, and affordable for women everywhere. Amphiphiles, which are surfactants that can act as detergents, have a long history as microbicides against many pathogens. Amphiphiles have several desirable traits; e.g., they are inexpensive, fast-acting, and capable of a broad spectrum of activity. An "ideal" amphiphilic microbicide will rapidly and selectively inactivate pathogens and sperm without irritating tissue. In this review, we discuss a homologous series of amphiphilic acylcarnitine analogues as microbicides. Two homologues, Z-14 and Z-15, possess excellent spermicidal, anti-HIV, anti-chlamydial, anti-gonorrhea, and anti-Haemophilus activities; both have outstanding anti-Candida activity. A 4% Z-15 gel that is comprised of 3% carboxymethylcellulose in water gives a dramatically low score in a rabbit-vaginal-irritation study. The mechanisms of action of these compounds are not fully understood as yet, but we present several possibilities. Moreover, the results of our limited structure-activity study with a homologous series have stimulated additional questions and ideas for designing the next generation of microbicidal amphiphiles. The above studies support the idea that Z-14 and Z-15 can potentially serve as safe (non-irritating), effective topical microbicides.
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PMID:Toward a design of affordable, topical microbicides: acylcarnitine analogues. 1630 10

Ceftobiprole (BAL9141) is an investigational cephalosporin active against methicillin- and vancomycin-resistant staphylococci administered as a water-soluble prodrug, ceftobiprole medocaril (BAL5788). Using an immunocompetent murine pneumonia model of Haemophilus influenzae, Enterobacter cloacae, or extended-spectrum beta-lactamase (ESBL) nonproducing or producing Klebsiella pneumoniae pneumonia, we compared results of treatment with ceftobiprole medocaril (71 mg/kg, sc, qid), ceftriaxone (50 mg/kg, im, bid), or cefepime (50 mg/kg, ip, q.i.d.). Results were expressed as median and 25th to 75th percentile log10 colony forming units per gram of lung tissue. Ceftobiprole, ceftriaxone, and cefepime were each more active than was no treatment and were equally active for treatment of experimental H. influenzae, E. cloacae, or ESBL-nonproducing K. pneumoniae pneumonia. For ESBL-producing K. pneumoniae, no differences were detected between no treatment and treatment with ceftobiprole, ceftriaxone, or cefepime. Ceftobiprole is active against H. influenzae, E. cloacae, and ESBL-nonproducing K. pneumoniae in an immunocompetent experimental murine pneumonia model.
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PMID:Ceftobiprole medocaril (BAL5788) treatment of experimental Haemophilus influenzae, Enterobacter cloacae, and Klebsiella pneumoniae murine pneumonia. 1663 39

Rhomboid peptidases are members of a family of regulated intramembrane peptidases that cleave the transmembrane segments of integral membrane proteins. Rhomboid peptidases have been shown to play a major role in developmental processes in Drosophila and in mitochondrial maintenance in yeast. Most recently, the function of rhomboid peptidases has been directly linked to apoptosis. We have solved the structure of the rhomboid peptidase from Haemophilus influenzae (hiGlpG) to 2.2-A resolution. The phasing for the crystals of hiGlpG was provided mainly by molecular replacement, by using the coordinates of the Escherichia coli rhomboid (ecGlpG). The structural results on these rhomboid peptidases have allowed us to speculate on the catalytic mechanism of substrate cleavage in a membranous environment. We have identified the relative disposition of the nucleophilic serine to the general base/acid function of the conserved histidine. Modeling a tetrapeptide substrate in the context of the rhomboid structure reveals an oxyanion hole comprising the side chain of a second conserved histidine and the main-chain NH of the nucleophilic serine residue. In both hiGlpG and ecGlpG structures, a water molecule occupies this oxyanion hole.
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PMID:The crystal structure of the rhomboid peptidase from Haemophilus influenzae provides insight into intramembrane proteolysis. 1721 Sep 13

Nontypeable Haemophilus influenzae (NTHI) strains are members of the normal human nasopharyngeal flora, as well as frequent opportunistic pathogens of both the upper and lower respiratory tracts. Recently, it has been shown that NTHI can form biofilms both in vitro and in vivo. NTHI strains within in vitro-formed biofilms differentially express both epitopes of lipooligosaccharide (LOS) and the outer membrane proteins P2, P5, and P6, whereas those generated either in a 96-well plate assay in vitro or in a mammalian host have been shown to incorporate a specific glycoform of sialylated LOS within the biofilm matrix. While DNA has been identified as a key component of the biofilm matrix formed in vitro by several bacterial pathogens, here we demonstrate for the first time that in addition to sialylated LOS, the biofilm formed by NTHI in vivo contains both type IV pilin protein and a significant amount of double-stranded DNA. The DNA appeared to be arranged in a dense interlaced meshwork of fine strands as well as in individual thicker "ropes" that span water channels, suggesting that DNA could be imparting structural stability to the biofilm produced by NTHI in vivo. The presence of type IV pilin protein both appearing as small aggregates within the biofilm matrix and tracking along DNA strands supports our observations which showed that type IV pili are expressed by NTHI during experimental otitis media when these bacteria form a biofilm in the middle ear space.
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PMID:Biofilms formed by nontypeable Haemophilus influenzae in vivo contain both double-stranded DNA and type IV pilin protein. 1732 18

Three experiments were done to evaluate some antibiotic therapies that are used commonly to treat pigs infected with Haemophilus pleuropneumoniae. Haemophilus-free piglets, 12 weeks of age, were challenged in a chamber with an aerosol of H. pleuropneumoniae serotype 1 and were medicated with antibiotics at various times before or after challenge. Antibiotic formulations which are commonly used to treat pneumonia in swine were used. They were chloramphenicol, penicillin, and a long-acting formulation of oxytetracycline given intramuscularly; and oxytetracycline, chloramphenicol and spiromycin (investigated as a potentially useful antibiotic) given in solution as the sole source of drinking water. Infection, disease (death, fever, gross lung lesions) and growth rate were measured in pigs following experimental challenge.The therapeutic effect of these antibiotic formulations was evaluated for prevention of the disease (52 pigs), treatment of acute disease (36 pigs), and treatment of chronic pneumonia (45 pigs). Injectable, long-acting oxytetracycline prevented all manifestations of disease (P<0.05) when given 24 hours before challenge. When treatment commenced immediately after the first signs of disease, each of the injected antibiotics reduced death rate (P<0.05), but they neither improved average daily gain nor reduced the incidence of infection and lung lesions. Chronically infected carrier pigs were produced by first immunizing them with a Haemophilus vaccine and then challenging them three weeks later. None of the treatments reduced the proportion of carriers of H. pleuropneumoniae.
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PMID:Comparison of common antibiotic therapies for haemophilus pleuropneumonia in pigs. 1742 81

The p-nitroaromatic antibiotic chloramphenicol has been used extensively to treat life-threatening infections due to Haemophilus influenzae and Neisseria meningitidis; its mechanism of action is the inhibition of protein synthesis. We found that during incubation with H. influenzae cells and lysates, chloramphenicol is converted to a 4-aminophenyl allylic alcohol that lacks antibacterial activity. The allylic alcohol moiety undergoes facile re-addition of water to restore the 1,3-diol, as well as further dehydration driven by the aromatic amine to form the iminoquinone. Several Neisseria species and most chloramphenicol-susceptible Haemophilus species, but not Escherichia coli or other gram-negative or gram-positive bacteria we examined, were also found to metabolize chloramphenicol. The products of chloramphenicol metabolism by species other than H. influenzae have not yet been characterized. The strains reducing the antibiotic were chloramphenicol susceptible, indicating that the pathway does not appear to mediate chloramphenicol resistance. The role of this novel nitroreductase pathway in the physiology of H. influenzae and Neisseria species is unknown. Further understanding of the H. influenzae chloramphenicol reduction pathway will contribute to our knowledge of the diversity of prokaryotic nitroreductase mechanisms.
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PMID:Chloramphenicol is a substrate for a novel nitroreductase pathway in Haemophilus influenzae. 1752 58

Histophilus somni (Haemophilus somnus) is an obligate inhabitant of the mucosal surfaces of bovines and sheep and an opportunistic pathogen responsible for respiratory disease, meningoencephalitis, myocarditis, arthritis, and other systemic infections. The identification of an exopolysaccharide produced by H. somni prompted us to evaluate whether the bacterium was capable of forming a biofilm. After growth in polyvinyl chloride wells a biofilm was formed by all strains examined, although most isolates from systemic sites produced more biofilm than commensal isolates from the prepuce. Biofilms of pneumonia isolate strain 2336 and commensal isolate strain 129Pt were grown in flow cells, followed by analysis by confocal laser scanning microscopy and scanning electron microscopy. Both strains formed biofilms that went through stages of attachment, growth, maturation, and detachment. However, strain 2336 produced a mature biofilm that consisted of thick, homogenous mound-shaped microcolonies encased in an amorphous extracellular matrix with profound water channels. In contrast, strain 129Pt formed a biofilm of cell clusters that were tower-shaped or distinct filamentous structures intertwined with each other by strands of extracellular matrix. The biofilm of strain 2336 had a mass and thickness that was 5- to 10-fold greater than that of strain 129Pt and covered 75 to 82% of the surface area, whereas the biofilm of strain 129Pt covered 35 to 40% of the surface area. Since H. somni is an obligate inhabitant of the bovine and ovine host, the formation of a biofilm may be crucial to its persistence in vivo, and our in vitro evidence suggests that formation of a more robust biofilm may provide a selective advantage for strains that cause systemic disease.
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PMID:Characterization and comparison of biofilm development by pathogenic and commensal isolates of Histophilus somni. 1764 81

Lipoprotein e (P4) from Haemophilus influenzae belongs to the "DDDD" superfamily of phosphohydrolases and is the prototype of class C nonspecific acid phosphatases. P4 is also a component of a H. influenzae vaccine. We report the crystal structures of recombinant P4 in the ligand-free and tungstate-inhibited forms, which are the first structures of a class C phosphatase. P4 has a two-domain architecture consisting of a core alpha/beta domain and a smaller alpha domain. The core domain features a five-stranded beta-sheet flanked by helices on both sides that is reminiscent of the haloacid dehalogenase superfamily. The alpha domain appears to be unique and plays roles in substrate binding and dimerization. The active site is solvent accessible and located in a cleft between the two domains. The structure shows that P4 is a metalloenzyme and that magnesium is the most likely metal ion in the crystalline recombinant enzyme. The ligands of the metal ion are the carboxyl groups of the first and third Asp residues of the DDDD motif, the backbone carbonyl of the second Asp of the DDDD motif, and two water molecules. The structure of the tungstate-bound enzyme suggests that Asp64 is the nucleophile that attacks the substrate P atom. Dimerization appears to be important for catalysis because intersubunit contacts stabilize the active site. Analysis of the structural context of mutations engineered for vaccine studies shows that the most promising mutations are located in the dimer interface. This observation suggests a structure-based vaccine design strategy in which the dimer interface is disrupted in order to expose epitopes that are buried in dimeric P4.
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PMID:Structure of recombinant Haemophilus influenzae e (P4) acid phosphatase reveals a new member of the haloacid dehalogenase superfamily. 1782 71

Diaminopimelate (DAP) epimerase catalyzes the stereoinversion of ll-DAP to meso-DAP, a precursor of l-lysine and an essential component of the bacterial peptidoglycan. This function is vital to bacteria and the enzyme therefore represents an attractive target for the design of novel anti-bacterials. DAP epimerase belongs to the group of PLP-independent amino acid racemases that function through a rather unusual mechanism involving two cysteines acting in concert as a base (thiolate) and an acid (thiol). We have solved the crystal structures of the apo-forms of DAP epimerase mutants (C73S and C217S) from Haemophilus influenzae at 2.3A and 2.2A resolution, respectively. These structures provide a snapshot of the enzyme in the first step of the catalytic cycle. Comparisons with the structures of the inhibitor-bound form reveal that the enzyme adopts an 'open conformation' in the absence of substrates or inhibitors with the two active site cysteines existing as a thiol-thiolate pair. Substrate binding to the C-terminal domain triggers the closure of the N-terminal domain coupled with tight encapsulation of the ligand, stabilization of the conformation of an active site loop containing Cys73 and expulsion of water molecules with concomitant desolvation of the thiolate base. This structural rearrangement is critical for catalysis.
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PMID:Dynamics of catalysis revealed from the crystal structures of mutants of diaminopimelate epimerase. 1788 30


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