Molecular determinants of the pathogenesis of disease due to non-typable<i>Haemophilus influenzae</i>

Rao, Venkatarama K.; Krasan, Graham P.; Hendrixson, David R.; Dawid, Suzanne; Geme, Joseph W. St.

doi:10.1111/j.1574-6976.1999.tb00393.x

Cited by 108 publications

(26 citation statements)

References 196 publications

(255 reference statements)

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“…The structure is shown in Figure 2; however, note that only the OS portion of the molecule was present in this sample. 4 As expected, glycosidic cleavages were prevalent and could be used to confirm the monosaccharide sequence. For example, the loss of a hexose (m/z 981), a heptose (m/z 951), and the Kdo moiety (m/z 923) from the precursor ion indicated that at least one hexose, heptose, and the Kdo must be in "terminating" positions.…”

Section: Ms N Analysis Of Sodiated Los and Os (Positive Ion Mode Detementioning

confidence: 83%

Mass Spectral Characterization of Lipooligosaccharides fromHaemophilus influenzae2019

et al. 2000

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Lipooligosaccharide (LOS) glycoforms from Haemophilus influenzae 2019 were profiled using the high-resolution and accurate mass capabilities of Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry. Sequence and linkage for two previously unknown LOS glycoforms were subsequently obtained through MSn analyses on FT-ICR and quadrupole ion trap (qIT) instruments. MSn analysis of negative ion precursors confirmed structural details within the lipid moiety, while CID spectra of sodiated precursor ions provided monosaccharide sequence and linkage for the oligosaccharide portion of the molecule. Results obtained in this study indicate that extensive heterogeneity exists within the oligosaccharide moieties in LOS from H. influenzae 2019. More importantly, the data suggest that additional hexose moieties, which are added onto the LOS, are not simple extensions of one particular core structure but rather that structural isomers with different connectivities are present within the heterogeneous mixture.

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Section: Ms N Analysis Of Sodiated Los and Os (Positive Ion Mode Detementioning

confidence: 83%

Mass Spectral Characterization of Lipooligosaccharides fromHaemophilus influenzae2019

et al. 2000

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“…The latter are defined by their failure to agglutinate with antisera against the recognized H. influenzae capsular polysaccharides and are referred to as nontypeable H. influenzae (NTHi). Encapsulated and nonencapsulated strains have similar morphological and metabolic properties, but they manifest differently in a clinical context (32). NTHi is a common cause of otitis media, sinusitis, and conjunctivitis (37), as well as chronic bronchitis, and is an important cause of communityacquired pneumonia.…”

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confidence: 99%

Glutathione-Dependent Alcohol Dehydrogenase AdhC Is Required for Defense against Nitrosative Stress in Haemophilus influenzae

et al. 2007

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In Haemophilus influenzae Rd KW20, we identified a gene, adhC, which encodes a class III alcohol dehydrogenase (AdhC) and has S-nitrosoglutathione reductase activity. adhC exists on an operon with estD, which encodes an esterase. Divergent to the adhC-estD operon is the Haemophilus influenzae nmlR gene (nmlR HI ), which encodes a MerR family regulator that is homologous to the Neisseria MerR-like regulator (NmlR). Analysis of an nmlR HI mutant indicated that expression of the adhC-estD operon is regulated by NmlR HI in strain Rd KW20. Chromosomal inactivation of either adhC or nmlR HI resulted in sensitivity to S-nitrosoglutathione and decreased S-nitrosoglutathione reductase activity. Examination of the NmlR HI -AdhC system in the genome sequences of nontypeable H. influenzae strains R2846, R2866, and 86-028NP identified significant variations. The adhC gene of 86-028NP was predicted to be nonfunctional due to a premature stop codon. Polymorphisms in the operator/promoter region of R2866 resulted in reduced enzyme activity. This correlated with an increased sensitivity to S-nitrosoglutathione. The adhC-nmlR HI system was examined in thirty-three clinical isolates (both capsular and nontypeable strains). Nucleic acid sequence data showed that only strain 86-028NP contained a premature stop codon. There were some variations in the DNA sequence of the operator/promoter region which altered the nmlR HI promoter. However, the clinical isolates still possessed S-nitrosoglutathione reductase activity and showed at least the equivalent ability to grow in the presence of S-nitrosoglutathione as Rd KW20. These data suggest that the nmlR HI -adhC system has a role in the defense against nitrosative stress in Haemophilus influenzae.

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“…NTHI lipooligosaccharide (LOS) is a major virulence determinant and may play a role in colonization and invasion of mucosal surfaces in the respiratory tract (3,16,23). NTHI LOS is analogous to the lipopolysaccharide (LPS) of enteric gramnegative bacteria in that it contains lipid A linked by 3-deoxy-D-manno-octulosonic acid to a heterogeneous sugar polymer (7).…”

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confidence: 99%

Evaluation of Phase Variation of Nontypeable Haemophilus influenzae Lipooligosaccharide during Nasopharyngeal Colonization and Development of Otitis Media in the Chinchilla Model

et al. 2000

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Nontypeable Haemophilus influenzae (NTHI) has four loci, lic-1 to lic-3 and lgtC, that generate phase-variable lipooligosaccharide (LOS) structures. lic-1, which is required for the expression of phosphorylcholine (ChoP), is the best characterized and is associated with an enhanced ability of H. influenzae to persist within the nasopharynges of infant rats. Recent data indicate that LOS impacts various aspects of NTHI virulence in the chinchilla model of nasopharyngeal colonization and otitis media (OM). In this study the effects of ChoP expression and the sequences of lic-1 to lic-3 and lgtC of NTHI strain 2019 were evaluated in the chinchilla OM model. Nasopharyngeal colonization data showed that a switch from the ChoP ؊ to the ChoP ؉ phenotype was observed as early as day 3 after intranasal inoculation. Chinchillas colonized by strains with the ChoP Otitis media (OM) or inflammation of the middle ear (ME), in one of its various clinical forms, is one of the most common childhood diseases. Nontypeable Haemophilus influenzae (NTHI) is a major OM pathogen and accounts for 25 to 30% of all cases of this disease. The initial event in the pathogenesis of NTHI OM is the colonization of the host mucosal surface; however, the bacterial factors that contribute to the colonization of the nasopharynx, retrograde ascension of the eustachian tube, and invasion of the ME during the natural progression of the disease are not well characterized. NTHI cells are frequently isolated from the upper respiratory tract, especially the nasopharynges of healthy children, with a reported rate of colonization of approximately 80% (8). Recent data suggested that there is a strong relationship between the frequency of colonization and the incidence of OM in children (5).NTHI lipooligosaccharide (LOS) is a major virulence determinant and may play a role in colonization and invasion of mucosal surfaces in the respiratory tract (3, 16, 23). NTHI LOS is analogous to the lipopolysaccharide (LPS) of enteric gramnegative bacteria in that it contains lipid A linked by 3-deoxy-D-manno-octulosonic acid to a heterogeneous sugar polymer (7). NTHI LOS, however, differs from classic enterobacterial LPS in that it does not contain repeating O-antigen units and is therefore more similar to that derived from Neisseria and Bordetella species (14). Moreover, H. influenzae cells demonstrate a propensity to alter or modulate their surface-expressed antigens including LOS (10, 12). NTHI cells express, on their outer surfaces, a number of LOS core oligosaccharide epitopes, and the expression of these epitopes is subject to frequent, reversible phase variation. Four chromosomal loci, lic-1 to lic-3 and lgtC, which contain long stretches of 4-bp tandem repeats within their 5Ј coding regions, have been reported to generate phase-variable LOS structures (9,11,19). lic-1 functions to add phosphorylcholine (ChoP) to the LOS molecule (22), lic-2 and lgtC are necessary for the expression of , and the effect of variation in lic-3 is unknown. Phase variation may represen...

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Molecular determinants of the pathogenesis of disease due to non-typableHaemophilus influenzae

Cited by 108 publications

References 196 publications

Mass Spectral Characterization of Lipooligosaccharides fromHaemophilus influenzae2019

Mass Spectral Characterization of Lipooligosaccharides fromHaemophilus influenzae2019

Glutathione-Dependent Alcohol Dehydrogenase AdhC Is Required for Defense against Nitrosative Stress in Haemophilus influenzae

Evaluation of Phase Variation of Nontypeable Haemophilus influenzae Lipooligosaccharide during Nasopharyngeal Colonization and Development of Otitis Media in the Chinchilla Model

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