The<i>Moraxella catarrhalis</i>Immunoglobulin D-Binding Protein MID Has Conserved Sequences and Is Regulated by a Mechanism Corresponding to Phase Variation

Möllenkvist, Andrea; Nordström, Therése; Halldén, Christer; Christensen, Jens Jørgen; Forsgren, Arne; Riesbeck, Kristian

doi:10.1128/jb.185.7.2285-2295.2003

Cited by 70 publications

(109 citation statements)

References 54 publications

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“…Interestingly, H. influenzae also displays a strong affinity for soluble human IgD (125), although the protein involved in IgD binding has as yet been identified only in M. catarrhalis. MID is also a B-lymphocyte mitogenic stimulant that initiates Ig production (49), and a comparison of MIDs of five strains revealed that the overall sequence identity ranged between 65.3% and 85.0%, with some regions showing an identity up to 97% (98).…”

Section: Adhesion and Major Ompsmentioning

confidence: 99%

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: Adhesion and Major Ompsmentioning

confidence: 99%

Molecular Aspects ofMoraxella catarrhalisPathogenesis

Vries

Bootsma

Hays

et al. 2009

Microbiol Mol Biol Rev

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“…The pellet was resuspended in Tris-HCl buffer containing 3% Empigen (Calbiochem) and protease inhibitors (Complete; Roche) (39). OMPs were extracted by rotating the mixture at 37°C for 2 h. The bacterial cells, stripped of their outer membranes, were centrifuged and supernatants collected.…”

Section: Omp Preparationsmentioning

confidence: 99%

Haemophilus influenzae Interacts with the Human Complement Inhibitor Factor H

Hallström

Zipfel

Blom

et al. 2008

The Journal of Immunology

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Pathogenic microbes acquire human complement inhibitors to circumvent the innate immune system. In this study, we identify two novel host-pathogen interactions, factor H (FH) and factor H-like protein 1 (FHL-1), the inhibitors of the alternative pathway that binds to Hib. A collection of clinical Haemophilus influenzae isolates was tested and the majority of encapsulated and unencapsulated bound FH. The isolate Hib 541 with a particularly high FH-binding was selected for detailed analysis. An increased survival in normal human serum was observed with Hib 541 as compared with the low FH-binding Hib 568. Interestingly, two binding domains were identified within FH; one binding site common to both FH and FHL-1 was located in the N-terminal short consensus repeat domains 6–7, whereas the other, specific for FH, was located in the C-terminal short consensus repeat domains 18–20. Importantly, both FH and FHL-1, when bound to the surface of Hib 541, retained cofactor activity as determined by analysis of C3b degradation. Two H. influenzae outer membrane proteins of ∼32 and 40 kDa were detected with radiolabeled FH in Far Western blot. Taken together, in addition to interactions with the classical, lectin, and terminal pathways, H. influenzae interferes with the alternative complement activation pathway by binding FH and FHL-1, and thereby reducing the complement-mediated bactericidal activity resulting in an increased survival. In contrast to incubation with active complement, H. influenzae had a reduced survival in FH-depleted human serum, thus demonstrating that FH mediates a protective role at the bacterial surface.

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“…The clinical M. catarrhalis isolates BBH18, RH4, and Bc5 have recently been described in detail (5,8). The M. catarrhalis strains were routinely cultured in brain heart infusion (BHI) liquid broth or on BHI agar plates at 37°C.…”

Section: Bacterial Strains and Culture Conditionsmentioning

confidence: 99%

“…3 and 4). The MID, also designated Hag (for hemagglutinin), has recently been demonstrated to function as an adhesin (5)(6)(7)(8)(9)(10)(11). Moreover, mice immunized with MID 764 -913 cleared M. catarrhalis much more efficiently as compared with mice immunized with BSA (12).…”

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

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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.

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

Cited by 70 publications

References 54 publications

Molecular Aspects ofMoraxella catarrhalisPathogenesis

Molecular Aspects ofMoraxella catarrhalisPathogenesis

Haemophilus influenzae Interacts with the Human Complement Inhibitor Factor H

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

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