The outer membrane proteins UspA1 and UspA2 of Moraxella catarrhalis are highly conserved in nasopharyngeal isolates from young children

Meier, Patricia Stutzmann; Troller, Rolf; Grivea, Ioanna N.; Syrogiannopoulos, George A.; Aebi, Christoph

doi:10.1016/s0264-410x(02)00030-0

Cited by 52 publications

(45 citation statements)

References 29 publications

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“…The uspA1 gene was found to be associated with adherent isolates (19) and could be detected in 87 to 99% of the isolates belonging to the seroresistant lineage, whereas only 23 to 36% of isolates belonging to the serosensitive lineage harbored the uspA1 gene (19,153). Further, it was demonstrated that all 16S rRNA type 1 isolates express UspA1, whereas this was not an inherited property of the 16S rRNA types 2/3 (94,150). No difference between the uspA2 genes of the seroresistant and serosensitive lineages was observed (19), which is contradictory to the fact that uspA2 is associated with serum resistance.…”

Section: M35 Porinmentioning

confidence: 94%

“…However, the phase-variable expression of important virulence factors, such as UspA1 (82), UspA2 (10), UspA2H (152), and MID/Hag (98), as well as the presence of immune evasion mechanisms, e.g., differences in OMP gene incidence, drift of LOS serotypes (150), and high genotypic heterogeneity, may have major implications for the development of a successful vaccine against M. catarrhalis. On the other hand, several virulence factors, such as the UspA family and MID/Hag, contain conserved and immunodominant regions, indicating that antigenic variation may play a more limited role in the immune response to vaccines based on these proteins (81,94). Nonetheless, current research indicates that a multivalent vaccine will be required to protect against M. catarrhalis colonization and pathogenesis.…”

Section: Concluding Remarks and Future Perspectivesmentioning

confidence: 99%

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Molecular Aspects ofMoraxella catarrhalisPathogenesis

Vries

Bootsma

Hays

et al. 2009

Microbiol Mol Biol Rev

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SUMMARY In recent years, Moraxella catarrhalis has established its position as an important human mucosal pathogen, no longer being regarded as just a commensal bacterium. Further, current research in the field has led to a better understanding of the molecular mechanisms involved in M. catarrhalis pathogenesis, including mechanisms associated with cellular adherence, target cell invasion, modulation of the host's immune response, and metabolism. Additionally, in order to be successful in the host, M. catarrhalis has to be able to interact and compete with the commensal flora and overcome stressful environmental conditions, such as nutrient limitation. In this review, we provide a timely overview of the current understanding of the molecular mechanisms associated with M. catarrhalis virulence and pathogenesis.

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Section: M35 Porinmentioning

confidence: 94%

Section: Concluding Remarks and Future Perspectivesmentioning

confidence: 99%

Molecular Aspects ofMoraxella catarrhalisPathogenesis

Vries

Bootsma

Hays

et al. 2009

Microbiol Mol Biol Rev

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“…The UspA2 protein is a putative autotransporter macromolecule that forms relatively short, filamentous projections on the surface of M. catarrhalis cells and is a target for biologically active antibodies [6,37]. In contrast to UspA1, it is not functioning as adhesin but is directly involved in the expression of serum resistance found in UspA2-positive Moraxella strains [5,38,39]. In addition, the results of the present study suggest that the UspA2-mediated activation of PKC controlling the NF-kB-dependent IL-8 release may represent a new virulence mechanism of Moraxella UspA2 in respiratory epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

“…This Gram-negative diplococcus colonises the lower respiratory tract of up to 32% of adults with COPD and is associated with recurrent and persistent lower respiratory tract infections that cause ,10% of all COPD exacerbations [3]. Among the various putative virulence factors of this pathogen that have been identified to date, several proteinaceous antigens have been shown to protrude from the outer membrane of M. catarrhalis, including the ubiquitous surface protein (Usp)A1 and UspA2 proteins, which are expressed in most clinical isolates [2,4,5]. In vitro mutant analysis indicates that UspA1 is involved in adherence to epithelial cells, whereas UspA2 is essential for serum resistance [6].…”

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confidence: 99%

Differential regulation of Moraxella catarrhalis-induced interleukin-8 response by protein kinase C isoforms

Slevogt

Maqami²,

Vardarowa³

et al. 2008

European Respiratory Journal

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Moraxella catarrhalis is a major cause of infectious exacerbations of chronic obstructive lung disease. In pulmonary epithelial cells, M. catarrhalis induces release of the proinflammatory cytokine interleukin (IL)-8, which plays a pivotal role in orchestrating airway inflammation.The present study demonstrated that protein kinase (PK)C was activated by Moraxella infection and positively regulated M. catarrhalis-triggered nuclear factor (NF)-kB activation and subsequent IL-8 release. Activation of the PKC/NF-kB signalling pathway was found to be dependent on expression of the Moraxella-specific ubiquitous surface protein A2. In addition, it was shown that specific isoforms of PKC play differential roles in the fine-tuning of the M. catarrhalis-induced NFkB-dependent gene expression through controlling il8 promoter activity. Inhibition of PKCa and e with chemical inhibitors or using short interfering RNA-mediated gene silencing significantly suppressed, whereas inhibition of PKCh increased, the M. catarrhalis-induced IL-8 transcription and cytokine release.In conclusion, it was shown that Moraxella catarrhalis infection activates protein kinase C and its isoforms a, e and h, which differentially regulate interleukin-8 transcription in human pulmonary epithelial cells.

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“…Of these, only UspA1 and UspA2H have been directly shown to mediate adherence to human cells (32,36). However, while UspA1 is expressed by virtually all strains tested to date, only ϳ20% of clinical isolates contain an uspA2H gene (32,37).…”

mentioning

confidence: 99%

Identification of aMoraxella catarrhalisOuter Membrane Protein Exhibiting Both Adhesin and Lipolytic Activities

Timpe¹,

Holm²,

Vanlerberg³

et al. 2003

Infect Immun

116

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The UspA1 and Hag proteins have previously been shown to be involved in the ability of the Moraxella catarrhalis wild-type strain O35E to bind to human Chang and A549 cells, respectively. In an effort to identify novel adhesins, we generated a plasmid library of M. catarrhalis DNA fragments, which was introduced into a nonadherent Escherichia coli strain. Recombinant E. coli bacteria were subsequently enriched for clones that gained the ability to bind to Chang and A549 cells, yielding the plasmid pELFOS190. The unencapsulated, gram-negative bacterium Moraxella catarrhalis is one of the leading causes of otitis media in young children and of lower respiratory tract infections in adults with chronic obstructive pulmonary disease (COPD). In developed countries, more than 80% of children under the age of 3 years will be diagnosed at least once with otitis media, and M. catarrhalis is responsible for 15 to 25% of all of these cases (6, 7, 10, 12, 26-29, 41, 51, 60). Lower respiratory tract infections (exacerbations) have been shown to contribute to the progression of COPD, and of the approximately 20 million cases of exacerbations documented each year in the United States, up to 35% result from M. catarrhalis infections (3,41,43,54,55).A vaccine that provides protection against M. catarrhalis is highly desirable due to this substantial morbidity as well as the growing concern over antibiotic resistance observed in clinical isolates (30). Toward this end, current research is focused on the identification of potential antigens with emphasis on the outer membrane proteins (OMPs) (26,34,35). While M. catarrhalis OMPs with a wide variety of functions have been identified, adhesins are particularly attractive vaccine candidates because they are surface-exposed antigens. Furthermore, adhesins generally play a crucial role in colonization and pathogenesis. For many bacteria, adherence to epithelial surfaces contributes to the evasion of host clearance mechanisms (4,25,59). Previous studies with M. catarrhalis have identified UspA1 (32, 36), UspA2 (2, 8, 36), Hag (14,15,17,19,24,45,47; M. M. Holm and E. R. Lafontaine, unpublished data), lipooligosaccharide (24), OMPCD (49), and UspA2H (32) as potential adhesins. Of these, only UspA1 and UspA2H have been directly shown to mediate adherence to human cells (32,36). However, while UspA1 is expressed by virtually all strains tested to date, only ϳ20% of clinical isolates contain an uspA2H gene (32, 37).The present study describes the identification of the novel M. catarrhalis OMP McaP. While this protein was identified based on its ability to function as an adhesin, we report that it also displays the enzymatic activity of an esterase and a phospholipase B (PLB). MATERIALS AND METHODSStrains, plasmids, tissue culture (TC) cell lines, and growth conditions. The bacterial strains and plasmids described in this study are listed in Table 1. M. catarrhalis was routinely cultured at 37°C on Todd-Hewitt medium (Difco). When cultured on agar plates, M. catarrhalis was incubated in an at...

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The outer membrane proteins UspA1 and UspA2 of Moraxella catarrhalis are highly conserved in nasopharyngeal isolates from young children

Cited by 52 publications

References 29 publications

Molecular Aspects ofMoraxella catarrhalisPathogenesis

Molecular Aspects ofMoraxella catarrhalisPathogenesis

Differential regulation of Moraxella catarrhalis-induced interleukin-8 response by protein kinase C isoforms

Identification of aMoraxella catarrhalisOuter Membrane Protein Exhibiting Both Adhesin and Lipolytic Activities

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