A novel cell-binding mechanism of Moraxella catarrhalis ubiquitous surface protein UspA: specific targeting of the N-domain of carcinoembryonic antigen-related cell adhesion molecules by UspA1

Hill, David J.; Virji, Mumtaz

doi:10.1046/j.1365-2958.2003.03433.x

Cited by 133 publications

(175 citation statements)

References 42 publications

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“…In this context, bacteria sharing ecological niches and lifestyles similar to pathogenic Neisseria could be interesting candidates to screen for CEACAM recognition. Indeed, several Gram-negative pathogens colonizing the human mucosa, such as M. catarrhalis and H. influenzae have evolved distinct surface antigens that are also able to engage human CEACAMs (Hill et al, 2001;Hill and Virji, 2003;Virji et al, 2000). As a large number of bacterial pathogens targets cellular receptors to establish an intimate contact with host cells, the described method might be a useful approach for analysing additional adhesin-receptor interaction pairs.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, binding of Opa CEA proteins to CEACAM3, a receptor present only on human granulocytes, results in recognition, efficient phagocytosis, and elimination of the bound pathogens (Schmitter et al, 2004). Interestingly, human Gram-negative pathogens apart from Neisseria, such as Haemophilus influenzae (Virji et al, 2000) and Moraxella catarrhalis (Hill and Virji, 2003) have also been shown to recognize CEACAMs by diverse adhesins. Accordingly, the analysis of the receptor binding profile of CEACAM-recognizing bacteria is critical to predict the potential cellular interactions mediated by these bacterial strains.…”

Section: Introductionmentioning

confidence: 99%

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Profiling of bacterial adhesin — host receptor recognition by soluble immunoglobulin superfamily domains

Kuespert¹,

Weibel²,

Hauck³

2007

Journal of Microbiological Methods

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Several Gram-negative human pathogens recognize members of the carcinoembryonic antigen-related cell adhesion molecule (CEACAM) family. Pathogenic Neisseriae employ distinct isoforms of the colony opacity-associated proteins (Opa CEA proteins) to bind to the amino-terminal domains of CEACAMs. Here we present a novel approach to rapidly determine the CEACAM-binding properties of single bacteria. Expression of the isolated amino-terminal domains of various CEACAMs in eukaryotic cells yields soluble probes that selectively recognize Opa CEA -expressing bacteria in a pull-down assay format. Furthermore, by expressing soluble CEACAMs as fusions to green-fluorescent protein (CEACAM-N-GFP), CEACAM-binding bacteria can be decorated with a fluorescent label and analysed by flow cytometry allowing the specific detection of receptor binding events on the level of single bacteria. Besides its potential for rapid and quantitative analysis of pathogen-receptor interactions, this novel approach allows the detection of receptor recognition in heterogeneous bacterial populations and might represent a valuable tool for profiling the host binding capabilities of various microorganisms.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Profiling of bacterial adhesin — host receptor recognition by soluble immunoglobulin superfamily domains

Kuespert¹,

Weibel²,

Hauck³

2007

Journal of Microbiological Methods

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“…Similarly, CEACAM-1-engaging adhesins have also been identified in M. catarrhalis. Ubiquitous surface protein A1 (UspA1), an outer membrane protein in M. catarrhalis, targets and interacts with CEACAM-1, facilitating adhesion and invasion of respiratory epithelium [39]. NTHi and M. catarrhalis induce the expression of their own receptor, CEACAM-1, on host cells, thereby increasing host susceptibility to bacterial infection [40].…”

Section: Temporal Host Surface Receptor Upregulation In Different Bodmentioning

confidence: 99%

“…Also, selective FimH-binding mannosides have been indicated in preventing UTIs in a preclinical murine model [106]. In vitro studies have found that anti-CEACAM antibodies block the adhesion of M. catarrhalis, N. meningitidis and NTHi to airway epithelial cells [39,71,107]. Also, NTHi adherence to A549 alveolar epithelial cells in vitro was shown to be inhibited in a dose-dependent manner with increasing concentrations of anti-ICAM-1 monoclonal antibodies [52].…”

Section: Inhibiting Specific Bacterial Adhesin-host Receptor Interactmentioning

confidence: 99%

Temporal upregulation of host surface receptors provides a window of opportunity for bacterial adhesion and disease

Shukla

Walters

et al. 2017

Microbiology

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Host surface receptors provide bacteria with a foothold from which to attach, colonize and, in some cases, invade tissue and elicit human disease. In this review, we discuss several key host receptors and cognate adhesins that function in bacterial pathogenesis. In particular, we examine the elevated expression of host surface receptors such as CEACAM-1, CEACAM-6, ICAM-1 and PAFR in response to specific stimuli. We explore how upregulated receptors, in turn, expose the host to a range of bacterial infections in the respiratory tract. It is apparent that exploitation of receptor induction for bacterial adherence is not unique to one body system, but is also observed in the central nervous, gastrointestinal and urogenital systems. Prokaryotic pathogens which utilize this mechanism for their infectivity include Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis and Escherichia coli. A number of approaches have been used, in both in vitro and in vivo experimental models, to inhibit bacterial attachment to temporally expressed host receptors. Some of these novel strategies may advance future targeted interventions for the prevention and treatment of bacterial disease.

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“…For example, the ubiquitous surface protein A (UspA)1 and UspA2 of M. catarrhalis directly bind and incapacitate C3 and further recruit complement inhibitors, such as C4b-binding protein (C4BP) and vitronectin (11)(12)(13). M. catarrhalis interacts with human carcinoembryonic Ag-related cell adhesion molecule 1 and integrin a5b1-associated fibronectin via UspAs to colonize the human respiratory tract epithelium (14,15). In addition, M. catarrhalis induces enhanced secretion of inflammatory cytokines by the respiratory epithelium, thus leading to amplification of airway inflammation and COPD exacerbations (16,17).…”

mentioning

confidence: 99%

Moraxella catarrhalis Evades Host Innate Immunity via Targeting Cartilage Oligomeric Matrix Protein

Liu

Gradstedt

Ermert

et al. 2016

The Journal of Immunology

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Moraxella catarrhalis is a respiratory tract pathogen commonly causing otitis media in children and acute exacerbations in patients suffering from chronic obstructive pulmonary disease. Cartilage oligomeric matrix protein (COMP) functions as a structural component in cartilage, as well as a regulator of complement activity. Importantly, COMP is detected in resident macrophages and monocytes, alveolar fluid, and the endothelium of blood vessels in lung tissue. We show that the majority of clinical isolates of M. catarrhalis (n = 49), but not other tested bacterial pathogens, bind large amounts of COMP. COMP interacts directly with the ubiquitous surface protein A2 of M. catarrhalis. Binding of COMP correlates with survival of M. catarrhalis in human serum by inhibiting bactericidal activity of the complement membrane attack complex. Moreover, COMP inhibits phagocytic killing of M. catarrhalis by human neutrophils. We further observed that COMP reduces bacterial adhesion and uptake by human lung epithelial cells, thus protecting M. catarrhalis from intracellular killing by epithelial cells. Taken together, our findings uncover a novel mechanism that M. catarrhalis uses to evade host innate immunity.

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A novel cell-binding mechanism of Moraxella catarrhalis ubiquitous surface protein UspA: specific targeting of the N-domain of carcinoembryonic antigen-related cell adhesion molecules by UspA1

Cited by 133 publications

References 42 publications

Profiling of bacterial adhesin — host receptor recognition by soluble immunoglobulin superfamily domains

Profiling of bacterial adhesin — host receptor recognition by soluble immunoglobulin superfamily domains

Temporal upregulation of host surface receptors provides a window of opportunity for bacterial adhesion and disease

Moraxella catarrhalis Evades Host Innate Immunity via Targeting Cartilage Oligomeric Matrix Protein

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