Vaccines for Moraxella catarrhalis

McMichael, John

doi:10.1016/s0264-410x(00)00287-5

Cited by 58 publications

(56 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…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].…”

mentioning

confidence: 99%

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

Slevogt

Maqami²,

Vardarowa³

et al. 2008

Eur Respir J

View full text Add to dashboard Cite

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.

show abstract

mentioning

confidence: 99%

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

Slevogt

Maqami²,

Vardarowa³

et al. 2008

Eur Respir J

View full text Add to dashboard Cite

show abstract

“…M. catarrhalis is also a common cause of sinusitis and lower respiratory tract infections in adults with chronic obstructive pulmonary disease. In recent years, focus has been on both its outer membrane protein composition and on its interactions with the human host (4). The outer membrane proteins of M. catarrhalis that are suggested as virulence determinants include, among others, Moraxella IgD binding protein (MID) 3 (3), catarrhalis outer membrane protein B (CopB), protein CD, M. catarrhalis adherence protein, and ubiquitous surface protein (Usp) (for reviews, see Refs.…”

mentioning

confidence: 99%

The Emerging Pathogen Moraxella catarrhalis Interacts with Complement Inhibitor C4b Binding Protein through Ubiquitous Surface Proteins A1 and A2

Nordström

Blom

Forsgren

et al. 2004

The Journal of Immunology

122

171

View full text Add to dashboard Cite

Moraxella catarrhalis ubiquitous surface protein A2 (UspA2) mediates resistance to the bactericidal activity of normal human serum. In this study, an interaction between the complement fluid phase regulator of the classical pathway, C4b binding protein (C4BP), and M. catarrhalis mutants lacking UspA1 and/or UspA2 was analyzed by flow cytometry and a RIA. Two clinical isolates of M. catarrhalis expressed UspA2 at a higher density than UspA1. The UspA1 mutants showed a decreased C4BP binding (37.6% reduction), whereas the UspA2-deficient Moraxella mutants displayed a strongly reduced (94.6%) C4BP binding compared with the wild type. In addition, experiments with recombinantly expressed UspA150–770 and UspA230–539 showed that C4BP (range, 1–1000 nM) bound to the two proteins in a dose-dependent manner. The equilibrium constants (KD) for the UspA150–770 and UspA230–539 interactions with a single subunit of C4BP were 13 μM and 1.1 μM, respectively. The main isoform of C4BP contains seven identical α-chains and one β-chain linked together with disulfide bridges, and the α-chains contain eight complement control protein (CCP) modules. The UspA1 and A2 bound to the α-chain of C4BP, and experiments with C4BP lacking CCP2, CCP5, or CCP7 showed that these three CCPs were important for the Usp binding. Importantly, C4BP bound to the surface of M. catarrhalis retained its cofactor activity as determined by analysis of C4b degradation. Taken together, M. catarrhalis interferes with the classical complement activation pathway by binding C4BP to UspA1 and UspA2.

show abstract

“…Several different M. catarrhalis outer membrane proteins (OMPs) have been isolated and more or less characterized (33). The best-defined group of moraxella OMPs is the ubiquitous surface protein A (UspA) family consisting of UspA1, UspA2 (HMWP), and UspA2H (1,13,27).…”

mentioning

confidence: 99%

TheMoraxella catarrhalisImmunoglobulin D-Binding Protein MID Has Conserved Sequences and Is Regulated by a Mechanism Corresponding to Phase Variation

Möllenkvist¹,

Nordström²,

Halldén

et al. 2003

J Bacteriol

103

View full text Add to dashboard Cite

Vaccines for Moraxella catarrhalis

Cited by 58 publications

References 45 publications

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

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

The Emerging Pathogen Moraxella catarrhalis Interacts with Complement Inhibitor C4b Binding Protein through Ubiquitous Surface Proteins A1 and A2

TheMoraxella catarrhalisImmunoglobulin D-Binding Protein MID Has Conserved Sequences and Is Regulated by a Mechanism Corresponding to Phase Variation

Contact Info

Product

Resources

About