Comparison of Moraxella catarrhalis isolates from children and adults for growth on modified New York City medium and potential virulence factors

Ahmer, Omar R. El; Braun, Jan-Matthias; Amyes, Sebastian G. B.; Weir, D. M.; Beuth, Josef; Blackwell, C. Caroline

doi:10.1099/jmm.0.05124-0

Cited by 14 publications

(12 citation statements)

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“…The fact that some strains of M. catarrhalis can resist serum killing was first described some 20 years ago by Winn and Morse (reviewed in references 10 and 50), and several recent studies indicate that the vast majority of M. catarrhalis isolates are resistant to serum killing (13,34,45). The identity of the gene product(s) responsible for this phenotype has been the subject of much research interest over the past decade, and it was first suggested by Verduin et al (54) that a proteinaceous substance on the surface of M. catarrhalis was responsible for complement resistance.…”

Section: Discussionmentioning

confidence: 99%

“…First observed about 20 years ago (reviewed in references 10 and 50), the occurrence of the serum-resistant phenotype has been documented in many subsequent studies of M. catarrhalis isolates (10,13,25,34,45,50,59). The hypothesis that serum resistance might be a virulence factor for M. catarrhalis stemmed from observations that the incidence of complement-resistant M. catarrhalis strains was higher in samples isolated from ill patients (i.e., adults with lower respiratory tract infections) than in samples from healthy adults or children (20,25).…”

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The UspA2 Protein of Moraxella catarrhalis Is Directly Involved in the Expression of Serum Resistance

et al. 2005

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Many strains of Moraxella catarrhalis are resistant to the bactericidal activity of normal human serum. Previous studies have shown that mutations involving the insertion of an antibiotic resistance cartridge into the M. catarrhalis uspA2 gene resulted in the conversion of a serum-resistant strain to a serum-sensitive phenotype. In the present study, the deletion of the entire uspA2 gene from the serum-resistant M. catarrhalis strain O35E resulted in a serum-sensitive phenotype and did not affect either the rate of growth or the lipooligosaccharide expression profile of this mutant. Inactivation of the classical complement pathway in normal human serum with Mg 2؉ and EGTA resulted in the survival of this uspA2 mutant. In contrast, blocking of the alternative complement pathway did not protect this uspA2 mutant from complement-mediated killing. To determine whether the UspA2 protein is directly involved in serum resistance, transformation and allelic exchange were used to replace the uspA2 gene in the serum-resistant strain O35E with the uspA2 gene from the serum-sensitive M. catarrhalis strain MC317. The resultant O35E transformant exhibited a serum-sensitive phenotype. Similarly, when the uspA2 gene from the serum-resistant strain O35E was used to replace the uspA2 gene in the serum-sensitive strain MC317, the MC317 transformant acquired serum resistance. The use of hybrid O35E-MC317 uspA2 genes showed that the N-terminal half of the O35E protein contained a 102-aminoacid region that was involved in the expression of serum resistance. In addition, when the uspA2 genes from strains O35E and MC317 were cloned and expressed in Haemophilus influenzae DB117, only the O35E UspA2 protein caused a significant increase in the serum resistance of the H. influenzae recombinant strain. These results prove that the UspA2 protein is directly involved in the expression of serum resistance by certain M. catarrhalis strains.Moraxella catarrhalis has gone from being regarded as a relatively harmless commensal organism found in the human nasopharynx to a pathogen which can cause a significant amount of disease (27,35,47,53). In the upper respiratory tract, M. catarrhalis is an important cause of otitis media in infants and young children (27). This unencapsulated, gramnegative bacterium can also cause infectious exacerbations of chronic obstructive pulmonary disease (46,47) and is an infrequent cause of other diseases, including pneumonia and sinusitis (reviewed in reference 35).Virtually nothing is known about the virulence mechanisms used by M. catarrhalis to produce disease. The lack of a relevant animal model for otitis media caused by this organism (27) has precluded direct investigation of this process at the experimental level. Numerous M. catarrhalis gene products that could be involved in the colonization of the human nasopharynx by this organism or in its ability to spread into other anatomic niches in the human body have been identified (reviewed in references 27 and 53), and recent studies have highlighted additional ...

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Section: Discussionmentioning

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The UspA2 Protein of Moraxella catarrhalis Is Directly Involved in the Expression of Serum Resistance

et al. 2005

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“…Both clinical and experimental reports indicated that the pro-inflammatory cytokines TNF-a, IL-1b, IL-6 and IL-8 were important mediators in OM; these were assessed for potential differences in their induction by the individual isolates of A. otitidis and in relation to the two colony types we described previously. 3 As virus infections are commonly associated with development of AOM 17 and can up-regulate cell surface antigens on the host cells that act as receptors for bacteria, [18][19][20] this important risk factor was examined in the model system. IFN-g is reported to differentiate and activate THP-1 cells.…”

Section: Introductionmentioning

confidence: 99%

In vitro inflammatory responses elicited by isolates of Alloiococcus otitidis obtained from children with otitis media with effusion

et al. 2013

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Alloiococcus otitidis is usually detected in children with otitis media (OM) by PCR as it is not often detected by routine culture. Our improved method for its isolation obtained A. otitidis from nearly 50% of 78 children with OM with effusion. The role of A. otitidis in pathogenesis of OM is unclear. This study tested two hypothesis: (1) that fresh isolates of A. otitidis would elicit pro-inflammatory cytokines from THP-1 monocytic cells equivalent to those induced by Streptococcus pneumoniae; (2) priming THP-1 cells with interferon-gamma (IFN-γ) a surrogate for virus infection, would enhance pro-inflammatory responses. Recent clinical isolates of A. otitidis, S. pneumoniae (ATCC 49619) and a blood culture isolate of S. pneumoniae (SP2) were used in the assays. Cytokines were quantified by BioRad bead assay and Luminex 200. IFN-γ priming enhanced cytokine responses. S. pneumoniae ATCC 49619 induced lower responses than SP2 for IL-1β, IL-6, TNF-α. A. otitidis LW 27 elicited higher IL-1β and TNF-α responses than either pneumococcal isolate. Small green colony types of A. otitidis induced higher responses than large white colony types for IL-8 and IL-1β. The hypothesis that A. otitidis elicits cytokines observed in middle ear effusions was supported; the need to use recent clinical isolates in studies of pathogenesis was highlighted.

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“…Other OMPs associated with virulence include the iron acquisition protein CopB (20), a hemagglutinin (28), and the lipooligosaccharide (44). Interestingly, there is increasing evidence to suggest that particular virulence traits are associated with distinct subpopulations of M. catarrhalis (8,12,42).Several OMPs of M. catarrhalis have been shown to elicit an antibody response in humans and have therefore been suggested as potential vaccine candidates; these include the immunoglobulin D-binding protein (15) and the major heat-modifiable protein Omp CD (31, 43). However, an ideal vaccine candidate has not yet been described.…”

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Identification and Characterization of a Novel Outer Membrane Protein (OMP J) of Moraxella catarrhalis That Exists in Two Major Forms

et al. 2005

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Moraxella catarrhalis is a common commensal of the human respiratory tract that has been associated with a number of disease states, including acute otitis media in children and exacerbations of chronic obstructive pulmonary disease in adults. During studies to investigate the outer membrane proteins of this bacterium, two novel major proteins, of approximately 19 kDa and 16 kDa (named OMP J1 and OMP J2, respectively), were identified. Further analysis indicated that these two proteins possessed almost identical gene sequences, apart from two insertion/deletion events in predicted external loops present within the putative barrel-like structure of the proteins. The development of a PCR screening strategy found a 100% (96/96) incidence for the genes encoding the OMP J1 and OMP J2 proteins within a set of geographically diverse M. catarrhalis isolates, as well as a significant association of OMP J1/OMP J2 with both the genetic lineage and the complement resistance phenotype (Fisher's exact test; P < 0.01). Experiments using two ⌬ompJ2 mutants (one complement resistant and the other complement sensitive) indicated that both were less easily cleared from the lungs of mice than were their isogenic wild-type counterparts, with a significant difference in bacterial clearance being observed for the complement-resistant isolate but not for its isogenic ⌬ompJ2 mutant (unpaired Student's t test; P < 0.001 and P ‫؍‬ 0.32). In this publication, we characterize a novel outer membrane protein of Moraxella catarrhalis which exists in two variant forms associated with particular genetic lineages, and both forms are suggested to contribute to bacterial clearance from the lungs.The gram-negative bacterium Moraxella catarrhalis is a common commensal of the human upper respiratory tract which has been associated with a number of disease states, including acute otitis media in children ( 9 , 14) and both acute and chronic bronchitis in adults (16,32). Nosocomial outbreaks of this pathogen have also been reported (10, 34), as well as cases of nearly fatal pneumonia (11). The morbidity burden of M. catarrhalis is particularly noticeable in young children suffering from recurrent otitis media episodes (13) and in adults presenting with chronic obstructive pulmonary disease (35).One particularly important virulence trait of M. catarrhalis is serum resistance (21), with several outer membrane proteins (OMPs) being implicated in the expression of this particular phenotype. Of particular importance is the UspA2 protein, a vitronectin binding protein whose N-terminal half may confer complement resistance on certain isolates (1,33,41). Other OMPs associated with virulence include the iron acquisition protein CopB (20), a hemagglutinin (28), and the lipooligosaccharide (44). Interestingly, there is increasing evidence to suggest that particular virulence traits are associated with distinct subpopulations of M. catarrhalis (8,12,42).Several OMPs of M. catarrhalis have been shown to elicit an antibody response in humans and have therefore been s...

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Comparison of Moraxella catarrhalis isolates from children and adults for growth on modified New York City medium and potential virulence factors

Cited by 14 publications

References 44 publications

The UspA2 Protein of Moraxella catarrhalis Is Directly Involved in the Expression of Serum Resistance

The UspA2 Protein of Moraxella catarrhalis Is Directly Involved in the Expression of Serum Resistance

In vitro inflammatory responses elicited by isolates of Alloiococcus otitidis obtained from children with otitis media with effusion

Identification and Characterization of a Novel Outer Membrane Protein (OMP J) of Moraxella catarrhalis That Exists in Two Major Forms

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