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)

Haemophilus influenzae undergoes phase variation in expression of the phosphorylcholine (ChoP) epitope, a structure present on several invasive pathogens residing in the human respiratory tract. In this study, structural analysis comparing organisms with and without this epitope confirmed that variants differ in the presence of ChoP on the cell surface-exposed outer core of the lipopolysaccharide. During nasopharyngeal carriage in infant rats, there was a gradual selection for H. influenzae variants that express ChoP. In addition, genotypic analysis of the molecular switch that controls phase variation predicted that the ChoP+ phenotype was predominant in H. influenzae in human respiratory tract secretions. However, ChoP+ variants of nontypable H. influenzae were more sensitive to the bactericidal activity of human serum unrelated to the presence of naturally acquired antibody to ChoP. Serum bactericidal activity required the binding of C-reactive protein (CRP) with subsequent activation of complement through the classical pathway. Results of this study suggested that the ability of H. influenzae to vary expression of this unusual bacterial structure may correlate with its ability both to persist on the mucosal surface (ChoP+ phenotype) and to cause invasive infection by evading innate immunity mediated by CRP (ChoP- phenotype).
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PMID:Phosphorylcholine on the lipopolysaccharide of Haemophilus influenzae contributes to persistence in the respiratory tract and sensitivity to serum killing mediated by C-reactive protein. 946 13

The antibody response to bacteria of the so-called HACEK group, i.e. Haemophilus spp., Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens and Kingella kingae, was measured in sera of six patients with endocarditis. The corresponding isolates from their blood cultures were identified by conventional methods, including reactions for nitrate reduction and catalase as well as acid production from sugars. Crude antigens were prepared by glycine extraction and sonification of the blood culture isolates, and used to determine titers by complement fixation. A patient with Haemophilus parainfluenzae bacteremia received a short course of antibiotic therapy, and relapsed with spondylitis and endocarditis 5 months later. Titers of sera against his own isolate rose from 1:40 to 1:320 and fell to 1:40 after therapy within one year. A patient with C. hominis endocarditis had a similarly prolonged course. The complement fixation titer against his own isolate was already 1:240 before antibiotics were administered. Another patient with C. hominis endocarditis presented a titer of 1:320 2 weeks after the diagnosis. These three patients revealed C-reactive protein values over 50 mg/l in the first serum sample. Decrease of both antibody titers and C-reactive protein values correlated with clinical improvement. Two patients with prosthetic valve replacement 5 months earlier developed C. hominis and K. kingae endocarditis, respectively. At admission, C-reactive protein values were 64 and 82, respectively, and therapy was instituted immediately. The first sera were received 3 and 6 weeks, respectively, after isolation of the corresponding blood culture isolates and revealed already low titers, i. e. 1:80 and 1:60, respectively. A woman with A. actinomycetemcomitans endocarditis received immediate therapy and did not develop titers against her own isolate. CRP was 100 at admission and remained over 50 5 weeks later. We conclude that the complement fixation assay with individual antigen preparations was easy to perform and allowed monitoring of the antibody response in 5 of 6 HACEK endocarditis cases under therapy, but the usefulness of this method to find culture-negative HACEK endocarditis needs to be established.
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PMID:Antibody response in six HACEK endocarditis cases under therapy. 967 92

The parameters C-reactive protein (CRP) and neopterin, which are associated with immunological reactions, were investigated in serum of healthy, diseased and with Haemophilus parasuis infected pigs. When comparing diseased young pigs with healthy young pigs significant increases of the CRP- and neopterin concentrations can be seen. The increase of the CRP-concentration was most remarkable. After the infection of SPF-piglets with Haemophilus parasuis, significantly decreased neopterin concentrations and increased CRP concentrations were determined in comparison with non-infected animals. The animals with the symptoms of arthritis and disorders of the central nervous system showed the lowest neopterin concentrations and the highest concentrations of CRP. It seems that CRP and neopterin are interesting serum parameters in pigs with regard to the recognition of immunological reactions after illness or infection.
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PMID:[Determination of C-reactive protein and neopterin in serum of diseased and bacterially infected swine]. 978 68

Phase variation in colony morphology has been associated with the pathogenesis of infection caused by Haemophilus influenzae. This study shows that differences in colony opacity in non-typeable H. influenzae (NTHi) strain H233 involve phase changes in the lipopolysaccharide (LPS) and depend on the expression of licl and lic2, which contain translational switches based on intragenic tandem repeats of 5'-CAAT-3'. Genetic analysis showed that opaque organisms have an out-of-frame number of repeats in both licl, required for the expression of phosphorylcholine (ChoP), and lic2, a putative galactosyl transferase that adds the terminal galactose on Galalpha1-4Gal. Defined variants in these loci were used to examine the contribution of individual LPS structures to resistance to serum bactericidal activity mediated by antibody and C-reactive protein (CRP). The addition of ChoP by licl was the only factor in serum killing involving CRP and complement. The terminal galactose moiety, in contrast, conferred resistance to killing by naturally acquired antibody and complement present in human serum. As Galalpha1-4Gal is also found on human glycolipids, it appears that decoration of the cell surface with this host-like antigen blocks antibody-mediated serum bactericidal activity. Genetic analysis of NTHi within the human respiratory tract demonstrated that Galalpha1-4Gal may not be expressed during carriage but may be advantageous for the organism in inflammatory states such as pneumonia.
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PMID:Adaptation of Haemophilus influenzae to acquired and innate humoral immunity based on phase variation of lipopolysaccharide. 1009 25

A retrospective analysis of 332 children with osteomyelitis (OM), managed from 1966 to 1996, was undertaken to evaluate etiology, clinical course and treatment results. In 64% of all patients positive bacterial cultures were obtained, Staphylococcus aureus, streptococci, pneumococci, and Haemophilus influenzae were the most frequently cultured pathogens. In two-thirds of the cases long bones (femur, tibia, humerus) were affected. Osteoarthritis or suppurative arthritis was evident in 27%; 32 of 170 (19%) re-evaluated patients had moderate or severe sequelae. Risk factors for an unfavorable course were the onset of disease in early infancy, suppurative arthritis, and an affected epiphysis. Suppurative arthritis, in particular, needs early evacuation to prevent sequelae. In recent years we observed an increasing number of patients presenting with atypical forms of OM. Since 1989 10 patients were considered to have chronic recurrent multifocal OM (CRMO). In 6 of them the clavicle was involved; their ages ranged from 3 to 14 years. The erythrocyte sedimentation rate was elevated (median 48, range 9-110 mm), while other inflammatory parameters like C-reactive protein (median 9, range <5-85 mg/l) or leucocyte count were slightly elevated or normal. Histopathology was stage-dependent, with a predominance of lymphoplasmacellular infiltration. A nonbacterial origin of CRMO is probable but not proven. Histopathology is not suitable for differentiation between bacterial and nonbacterial forms of bone inflammation.
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PMID:Changing pattern of osteomyelitis in infants and children. 1041 87

The lic1 locus of Haemophilus influenzae controls the incorporation of environmental choline into lipopolysaccharide (LPS) as phosphorylcholine (ChoP) as well as the phase variation of this structure. ChoP is the target of an acute phase reactant in serum, C-reactive protein (CRP), which mediates killing through the activation of complement when bound to the organism. Structural analysis of the oligosaccharide region of the H. influenzae LPS showed that ChoP is linked to different hexose residues on different chain extensions in strains Rd and Eagan. Differences in the molecular environment of ChoP affect the epitope defined by monoclonal antibody 12D9 and were associated with polymorphisms within LicD, a putative diphosphonucleoside choline transferase. Exchanging the licD genes between the two strains with ChoP on different chain extensions was sufficient to switch its position. Allelic variants with ChoP on a hexose on heptose III rather than heptose I were sensitive to CRP-mediated serum bactericidal activity regardless of the genetic background. Differences in CRP-mediated killing correlated with differences in the binding of CRP from human serum to whole bacteria. This suggests that, in addition to the mechanism involving phase variation, the structural rearrangements within the oligosaccharide contribute to evasion of innate and acquired immunity.
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PMID:The position of phosphorylcholine on the lipopolysaccharide of Haemophilus influenzae affects binding and sensitivity to C-reactive protein-mediated killing. 1063 93

Phosphorylcholine (ChoP) is a potential candidate for a plurispecific vaccine, because it is present on surface components of many mucosal organisms, including Haemophilus influenzae, Streptococcus pneumoniae and Pseudomonas aeruginosa. In addition, ChoP has been detected on pili of Neisseria meningitidis and Neisseria gonorrhoeae. In this study, we demonstrate the presence of the phosphorylcholine epitope on the lipopolysaccharides (LPSs) of several species of commensal Neisseriae (Cn), a property that differentiates commensal from the pathogenic strains of Neisseriae. In an extended survey of 78 strains, we confirmed the exclusive expression of the ChoP epitope on pili of pathogenic Neisseriae. Despite the presence of pili on Cn, which are homologous to Class II pili of N. meningitidis, they did not react with anti-ChoP antibody. This observation was further supported by the fact that 14C-labelled choline was incorporated only in the LPSs of Cn. Analysis of the LPS of N. lactamica strain NL4 revealed two distinct and interconvertible molecular species of LPS with high and low levels of reactivity with anti-ChoP antibody. In addition, on/off phase variation gave rise to frequent modulation in the levels of antibody reactivity. A concurrent modulation was also observed in the binding of C-reactive protein, CRP, a ChoP-binding reactant that is implicated in bacterial clearance. Genetic analysis showed the presence of a gene in several Cn spp. with significant sequence identity to H. influenzae licA. This gene encodes choline kinase and is also involved in phase variation of the LPS-associated ChoP in H. influenzae. In contrast, licA-like genes were not identified in the pathogenic Neisseria strains tested. They are absent from N. meningitidis strain Z2491 genome database. These data suggest that the genetic basis for ChoP incorporation in Cn LPS resembles that in H. influenzae spp. and may be distinct from that generating the ChoP epitope on pili of pathogenic Neisseriae. Further, the modulation of ChoP expression on Cn LPS, and corresponding modulation of CRP binding, has the potential to confer the property of immune avoidance and thus of persistence on mucosa.
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PMID:Phosphorylcholine decoration of lipopolysaccharide differentiates commensal Neisseriae from pathogenic strains: identification of licA-type genes in commensal Neisseriae. 1076 Jan 54

The effect of phase variation of lipopolysaccharide (LPS) structure on the susceptibility of Haemophilus influenzae to complement-dependent killing by normal human sera and normal rat sera has been described previously. The phase-variable structure phosphorylcholine (ChoP) confers susceptibility to human serum, since ChoP on the bacterial cell surface binds to serum C-reactive protein and activates complement. In contrast, expression of galalpha1,4gal, a second phase-variable epitope that is also found on human glycoconjugates, confers resistance to human serum. We studied the role of phase variation of these structures in the susceptibilities of H. influenzae KW20 (Rd) and a clinical isolate of nontypeable H. influenzae to killing by rabbit sera, which often possess naturally acquired complement-dependent bactericidal activity for unencapsulated H. influenzae. Expression of ChoP increased the resistance of strain KW20 to killing by bactericidal rabbit sera. In contrast, the serum resistance of a clinical isolate, H233, was unaffected by ChoP expression but was reduced by galalpha1,4gal expression. The rabbit sera with bactericidal activity (but not the nonbactericidal sera) all contained immunoglobulin M (IgM) antibodies able to bind to the surface of H. influenzae bacteria, as detected by flow cytometry, and contained IgM antibodies to LPS purified from strain KW20. Preincubation of sera with LPS reduced their bactericidal activity. Bactericidal activity was recovered quantitatively in an IgM-enriched fraction of sera. It is concluded that naturally occurring bactericidal activity for unencapsulated H. influenzae is largely due to IgM antibodies directed against phase-variable structures of the LPS.
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PMID:Role of lipopolysaccharide phase variation in susceptibility of Haemophilus influenzae to bactericidal immunoglobulin M antibodies in rabbit sera. 1076 76

C-reactive protein (CRP) is a normal constituent of human sera synthesized by hepatocytes and induced by proinflammatory cytokines. The function of this acute-phase reactant includes activation of complement and enhancement of opsonophagocytosis. CRP binds to phosphorylcholine (ChoP), a constituent of eukaryotic membranes that is also found on the cell surface of major bacterial pathogens of the human respiratory tract, including Streptococcus pneumoniae and Haemophilus influenzae. The presence of CRP on mucosal surfaces and role in innate immunity in the human respiratory tract where ChoP-containing organisms reside have not been previously studied. We have shown using a monoclonal antibody to CRP that CRP is present in inflamed (0.17 to 42 microg/ml) and uninflamed (<0.05 to 0.88 microg/ml) secretions from the human respiratory tract in sufficient quantities for an antimicrobial effect. In addition, the CRP gene was expressed in epithelial cells of the human respiratory tract using in situ hybridization on nasal polyps and reverse transcriptase PCR of pharyngeal cells in culture. The complement-dependent bactericidal activity of normal nasal airway surface fluid and sputum against ChoP-expressing H. influenzae was abolished when the secretions were pretreated to remove CRP. In summary, the results indicate that CRP is present in secretions of the human respiratory tract, that human respiratory epithelial cells are capable of CRP expression, and that this protein may contribute to bacterial clearance in the human respiratory tract.
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PMID:Expression of C-reactive protein in the human respiratory tract. 1117 52

Acute hematogenous osteomyelitis in children is a relatively uncommon but potentially serious disease. Improvements in radiologic imaging, most notably magnetic resonance imaging, and a heightened awareness of this condition have led to earlier detection and resultant marked decreases in morbidity and mortality. Staphylococcus aureus, which has the ability to bind to cartilage, produce a protective glycocalyx, and stimulate the release of endotoxins, accounts for 90% of infections in all age groups. Infections with Haemophilus influenzae have become rare in immunized children. A careful history and a thorough physical examination remain important. Positive cultures are obtained in only 50% to 80% of cases; the yield is improved by the use of blood cultures and evolving molecular techniques. Improvements in antibiotic treatment have lessened the role of surgery in managing these infections. Sequential intravenous and high-dose oral antibiotic therapy is now an accepted modality. Evaluation of response to treatment by monitoring C-reactive protein levels has decreased the average duration of therapy to 3 to 4 weeks with few relapses. The emergence of antibiotic resistance, particularly resistance to methicillin and vancomycin by S aureus organisms, is of increasing concern. Long-term sequelae and morbidity are primarily due to delays in diagnosis and inadequate treatment.
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PMID:Acute hematogenous osteomyelitis in children. 1142 74


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