Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:O75191 (H. influenzae)
 4,961 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serial sputum isolates of Haemophilus influenzae (n = 69) were obtained from eight patients suffering from cystic fibrosis. For two of these patients all strains were analysed for polymorphism in the major outer membrane protein profile. For all patients the strains were genetically characterised by random amplification of polymorphic DNA analysis. All strains were included in a survey for polymorphism in regions containing moieties of repetitive DNA as well. A single locus containing trinucleotide repeat units, three loci harbouring tetranucleotides, one region comprising pentanucleotide units and two hexanucleotide repeat unit-containing loci were analysed for repeat number variability. Most of the regions were previously shown to be directly adjacent to or even within virulence genes. All regions behaved as genuine variable number of tandem repeat loci in the sense that genetic polymorphism based on the presence of varying numbers of repeat units could be demonstrated among different strains. Interestingly, several of the repeats showed variation in the absence of the variability as assessed by major outer membrane protein or random amplification of polymorphic DNA analysis. These observations indicate that the repeat loci may vary independently from major chromosomal polymorphism. Consequently, H. influenzae appears to modify its virulence gene regions of the chromosome during persistent colonisation of the lung in cystic fibrosis patients.
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PMID:Variable numbers of tandem repeat loci in genetically homogeneous Haemophilus influenzae strains alter during persistent colonisation of cystic fibrosis patients. 1022 Aug 86

Nonencapsulated Haemophilus influenzae frequently persists in the lungs of chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF) patients for prolonged periods of time. The bacteria are not eradicated by antibiotic treatment of the patients or by specific antibodies that are found in the sputum and sera of these patients. We investigated whether H. influenzae, when localized in lung epithelial cell layers, is shielded from antibiotics and from antibody-mediated bactericidal activity of specific antibodies. An in vitro model system consisting of lung epithelial NCI-H292 cells on permeable supports was developed to allow long term association of H. influenzae with the cells. Microscopic examination showed increasing numbers of H. influenzae bacteria between the epithelial cells up to 24 h of incubation. Coinciding with the microscopic observations the maximum number of cell-associated bacteria surviving gentamicin treatment of the cell layers was obtained after 24 h of incubation. All H. influenzae strains, and one Haemophilus parainfluenzae strain tested penetrated into the cell layer as determined by gentamicin killing. Cell-associated bacteria were shielded from the bactericidal activity of several antibiotics and from antibody-mediated bactericidal activity. After prolonged incubation in the cell system in the presence of a specific bactericidal antibody against major outer membrane protein (MOMP) P2, antigenic variation occurred due to a point mutation in the MOMP P2 gene, similar to point mutations observed in vivo. We conclude that penetration of H. influenzae between lung epithelial cells results in shielding the bacteria from killing by antibody dependent defense mechanisms and by antibiotics. Therefore, penetration of H. influenzae between epithelial cells may contribute to the persistence of this microorganism in COPD and CF patients.
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PMID:Haemophilus influenzae localized in epithelial cell layers is shielded from antibiotics and antibody-mediated bactericidal activity. 1022 10

The nature of the micro-flora present in sputa of six different cystic fibrosis (CF) patients was assessed using routine microbiological culture and molecular methods. Bacterial genes for the small subunit ribosomal RNA (ssu rDNA) were specifically amplified from DNA extracted from the sputum samples, cloned and characterised by hybridisation and DNA sequencing. A large number of clones from six sputa were screened. Initially, oligonucleotide hybridisation was performed with five probes, specific for Gram-positives and Gram-negatives in general and the main pathogens for the CF patient (Staphylococcus aureus, Pseudomonas aeruginosa and Haemophilus influenzae). For a single sputum sample, the results were fully congruent when culture and molecular methods were compared. In the other five sputa, discrepancies for S. aureus and/or H. influenzae were documented. Although S. aureus DNA and H. influenzae DNA was detected in three and four sputa, respectively, strains could not be cultured. Although the PCR approach is not capable of distinguishing viable from dead bacteria, all of the CF patients had a history of S. aureus infections, while one of the CF patients once had cultivable H. influenzae in the sputum as well. A number of clones for probe-unidentified Gram-negative or Gram-positive bacterial species were further analysed by sequencing and additional potential pathogens were identified. Although routine culture of sputum frequently points to mono-specific exacerbations, our molecular data indicate that the other CF-related pathogens appear to be persistently present as well. We conclude that routine culture for bacterial pathogens from CF sputa yields limited microbiological information since it frequently fails to identify a number of pathogenic bacterial species that are potentially present in a viable status in the lungs of these patients.
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PMID:Comparison of conventional and molecular methods for the detection of bacterial pathogens in sputum samples from cystic fibrosis patients. 1061 90

A prospective, randomised, single-blind comparative trial was carried out to determine whether double beta-lactam treatment with pivampicillin plus pivmecillinam is more effective than pivampicillin alone in the treatment of recurrent and chronic lung infections with Haemophilus influenzae in patients with chronic obstructive pulmonary disease (COPD) or cystic fibrosis (CF). Fifty-six children and young adults with COPD or CF were randomised to the clinical study. The patients were allocated at random to receive perorally either pivmecillinam, 40 mg/kg/day, combined with pivampicillin, 50 mg/kg/day, or pivampicillin 50 mg/kg/day alone for 14 days. A cross-over pharmacokinetic study using the same drugs was carried out in 10 CF patients to determine the antibiotic concentrations in serum and sputum after a single dose of each drug. The clinical study showed no significant differences in clinical scoring, lung function tests or adverse events after treatment with pivampicillin plus pivmecillinam or pivampicillin alone. Follow-up microbiological evaluation 2 and 6 weeks after the end of treatment showed that the offending pathogen was eradicated in 68% of the patients treated with pivampicillin plus pivmecillinam and in 67% of the patients treated with pivampicillin alone. Reinfection with another biotype was more common in the combination group (50% vs. 21%) than in the pivampicillin group. In the pharmacokinetic study the median peak serum concentration occurred two hours after intake of tablets. The efficacy of double beta lactam treatment in lung infections with H. influenzae appears to be equivalent to that of ampicillin on clinical lung symptoms, lung function tests, adverse effects and bacteriology.
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PMID:Randomised trial of pivampicillin plus pivmecillinam vs. pivampicillin in children and young adults with chronic obstructive pulmonary disease and infection with Haemophilus influenzae. 1064 Feb 63

We report on the rapid and specific detection of bacteria commonly isolated from clinical specimens from cystic fibrosis (CF) patients by fluorescent in situ hybridization (FISH). On the basis of comparative sequence analysis, we designed oligonucleotide probes complementary to species-specific 16S rRNA regions of these microorganisms and demonstrated the specificities of the probes by hybridization of different remotely related as well as closely related reference strains. Furthermore, in a pilot project we investigated 75 sputum samples and 10 throat swab specimens from CF patients by FISH and detected Pseudomonas aeruginosa, Burkholderia cepacia, Stenotrophomonas maltophilia, Haemophilus influenzae, and Staphylococcus aureus within these specimens. The specificity of FISH was 100% in comparison to the results of conventional microbial culture. In contrast, the sensitivity of standard laboratory cultivation was moderately higher, since the limit for microscopic detection of bacteria within sputum samples by FISH was approximately 4 x 10(5) CFU/ml of sputum (resulting in a 90% sensitivity for FISH). Moreover, we demonstrated that FISH will be useful for the rapid detection of bacteria that cause acute pulmonary exacerbations in CF patients, as demonstrated in patients with H. influenzae, S. aureus, and P. aeruginosa exacerbations. Therefore, FISH is a valuable additional method for the rapid and specific detection of bacteria in clinical samples from CF patients, in particular, patients with pulmonary exacerbations.
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PMID:Specific and rapid detection by fluorescent in situ hybridization of bacteria in clinical samples obtained from cystic fibrosis patients. 1065 91

Changes in amino-acid sequence of the unique pore-forming protein of H. influenzae (OmpP2; porin) have been associated with increased antimicrobial resistance in H. influenzae strains isolated from cystic fibrosis patients. From patients who were subjected to long-term antimicrobial therapy, H. influenzae strains 67d and 69a (patient 27) and strains 77a and 77f (patient 30) were isolated. Strains 67d and 77a were previously shown to have elevated values for minimal inhibitory concentrations of antibiotics compared to strains 69a and 77f. Porins were extracted from all four H. influenzae strains by detergent treatment and purified to homogeneity by ion exchange chromatography. By reconstitution of the clinical Hi porins into planar lipid bilayers, single-channel conductance, ionic selectivity, and voltage-gating characteristics were assessed. Porins 77a and 77f displayed similar single-channel conductance and ionic selectivity. Current-voltage relationships were determined for the different porins: porin 77f displayed substantial voltage gating at both positive and negative polarity; porin 77a gated at negative polarity only. Porins 67d and 69a showed substantial differences in their pore-forming properties: the single-channel conductance of porin 69a was significantly increased (1.05 nS) relative to porin 67d (0.73 nS). Porin 67d was twice as permeable to cations as porin 69a, and at both positive and negative polarities the extent of voltage gating was greater for porin 67d relative to porin 69a. Expression of the porins in an isogenic, porin-deleted H. influenzae background allowed for assessment of the contribution of each porin to the minimum inhibitory concentrations of various antimicrobial compounds. Porin 67d was found to have a decreased susceptibility to the antimicrobials novobiocin and streptomycin. This decreased susceptibility of porin 67d to novobiocin and streptomycin correlates with its decrease in single-channel conductance.
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PMID:Altered channel properties of porins from Haemophilus influenzae: isolates from cystic fibrosis patients. 1223 88

Microorganisms such as Pseudomonas aeruginosa, Staphylococcus aureus and Haemophilus influenzae frequently cause colonization and infection in airways of patients with cystic fibrosis. Burkholderia cepacia has also been isolated in patients with cystic fibrosis since 1980. In this study, we aimed to determine the colonization rate of B. cepacia in 286 sputum samples obtained from 129 cystic fibrosis patients. Selective media for B. cepacia were used besides the routine microbiological media in order to increase the isolation rate. The colonies were identified by biochemical tests and the antibiotic susceptibilities of the strains were determined by disc diffusion method. Pathogenic bacteria (S. aureus, P. aeruginosa, Enterobacteriaceae, Streptococcus pneumoniae, H. influenzae) were isolated in 52 of 129 patients (40%) and 66 of 286 sputum samples (23%). In addition 2 B. cepacia strains were isolated from two different patients (1.55%). B. cepacia is now being considered as a pathogen isolated from sputum samples of patients with cystic fibrosis with an increasing frequency and causing severe clinical features. According to these results it can be concluded that, the use of selective media for B. cepacia isolation, should be taken into consideration especially by the clinical microbiology laboratories collaborating with the cystic fibrosis centers.
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PMID:[Isolation frequency of Burkholderia cepacia from cystic fibrosis patients]. 1247 60

Recent bronchoscopy studies using assays to measure inflammation and molecular typing techniques have facilitated an increased understanding of the early events that occur within the lungs of young children with cystic fibrosis and provided additional insights into the natural history of lung disease in children. In 2000, the US CF National Patient Registry data showed that among 1000 infants <2 years of age, the first bacterial pathogens detected are Haemophilus influenzae, Staphylococcus aureus, and Pseudomonas aeruginosa and the prevalence of these pathogens in these young infants are 19%, 42%, and 29%, respectively. In addition, 7% harbour Stenotrophomonas maltophilia and <1% harbour Burkholderia cepacia complex. Several investigators have performed bronchoscopy studies on young infants to further examine the natural history of lung disease. In one such study of 40 CF infants, 65%, 63% and 70% of children at 1, 2, and 3 years of age harboured at least one CF pathogen. H. influenzae was most common (38%) in infants at 1 year of age, and S. aureus was most common in 2 (37%) and 3 (36%) year olds. P. aeruginosa increased from 18% at 1 year of age to 33% at 3 years of age and was usually present in high numbers, i.e., > or =10(5) CFU/ml of BAL fluid. Investigators have studied the microbiology of young CF infants using specimens derived from the upper airway (deep throat) compared with the lower airway (broncheoalveolar lavage specimens) to determine if the upper airway is predictive of pathogens in the lower airway. In general, these studies have shown that a negative oropharyngeal culture indicated that isolation of P. aeruginosa from the lower airway was unlikely, but a positive culture did not predict lower airway infection. Similar findings were noted for H. influenzae and S. aureus.
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PMID:Microbiology of early CF lung disease. 1498 Feb 98

The persistence and variability of 188 Haemophilus influenzae isolates in respiratory tract of 30 cystic fibrosis (CF) patients over the course of 7 years was studied. Antibiotic susceptibility testing, DNA fingerprinting, and analysis of outer membrane protein profiles were performed on all isolates. A total of 115 distinct pulsed-field gel electrophoresis profiles were identified. Ninety percent of patients were cocolonized with two or more clones over the studied period. A third of the patients were cross-colonized with one or two H. influenzae strains; 11% of the clones persisted for 3 or more months. Biotype, outer membrane protein profiles, and resistance profiles showed variation along the studied period, even in persisting clones. Four isolates (2.1%) recovered from 3 patients were type f capsulate, with three of them belonging to the same clone. beta-Lactamase production was detected in 23.9% of isolates while 7% of the beta-lactamase-negative isolates presented diminished susceptibility to ampicillin (beta-lactamase-negative ampicillin resistance phenotype). Remarkably, 21.3% of the H. influenzae isolates presented decreased susceptibility to ciprofloxacin, which was mainly observed in persisting clones. Of the H. influenzae isolates from CF patients, 18 (14.5%) were found to be hypermutable in comparison with 1 (1.4%) from non-CF patients (P < 0.0001). Ten patients (33.3%) were colonized by hypermutable strains over the study period. A multiresistance phenotype and long-term clonal persistence were significantly associated in some cases for up to 7 years. These results suggest that H. influenzae bronchial colonization in CF patients is a dynamic process, but better-adapted clones can persist for long periods of time.
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PMID:Dynamics of long-term colonization of respiratory tract by Haemophilus influenzae in cystic fibrosis patients shows a marked increase in hypermutable strains. 1507 Sep 88

Hypermutable bacterial pathogens exist at surprisingly high prevalence and benefit bacterial populations by promoting adaptation to selective environments, including resistance to antibiotics. Five hundred Haemophilus influenzae isolates were screened for an increased frequency of mutation to resistance to rifampicin, nalidixic acid and spectinomycin: of the 14 hypermutable isolates identified, 12 were isolated from cystic fibrosis (CF) sputum. Analysis by enterobacterial repetitive intergenic consensus (ERIC)-PCR and ribotyping identified eight distinct genetic fingerprints. The hypermutable phenotype of seven of the eight unique isolates was associated with polymorphisms in conserved sites of mutS. Four of the mutant mutS alleles were cloned and failed to complement the mutator phenotype of a mutS : : TSTE mutant of H. influenzae strain Rd KW20. Antibiotic susceptibility testing of the hypermutators identified one beta-lactamase-negative ampicillin-resistant (BLNAR) isolate with two isolates producing beta-lactamase. Six isolates from the same patient with CF, with the same genetic fingerprint, were clonal by multilocus sequence typing (MLST). In this clone, there was an evolution to higher MIC values for the antibiotics administered to the patient during the period in which the strains were isolated. Hypermutable H. influenzae with mutations in mutS are prevalent, particularly in the CF lung environment, and may be selected for and maintained by antibiotic pressure.
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PMID:Hypermutable Haemophilus influenzae with mutations in mutS are found in cystic fibrosis sputum. 1534 53


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