Outer membrane protein <scp>P</scp>1 is the <scp>CEACAM</scp>‐binding adhesin of <scp><i>H</i></scp><i>aemophilus influenzae</i>

Tchoupa, Arnaud Kengmo; Lichtenegger, Sabine; Reidl, Joachim; Hauck, Christof R.

doi:10.1111/mmi.13134

Cited by 36 publications

(45 citation statements)

References 45 publications

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“…Similar to Neisseria species, the gram-negative coccobacillus Haemophilus influenzae also expresses a specific outer membrane protein, namely OMP P1, that targets the IgV domain of CEACAM1 in a grossly isolate-independent manner [58]. In contrast, the CEACAM3 IgV and CEACAM5 IgV also bind OMP P1 but only in fraction (~25%) of studied isolates suggesting that OMP P1 has co-evolved with CEACAM1 as its primary binding partner [58]. This reflects the significance of the OMP P1-CEACAM1 IgV interaction but more importantly emphasizes the highly specific nature of OMP P1 by which CEACAM1 is the major preferred CEACAM family member.…”

Section: Ceacam1 Igv Heterophilic Interactions With Host Ligands-thementioning

confidence: 99%

CEACAM1 structure and function in immunity and its therapeutic implications

Kim

Huang

Gandhi

et al. 2019

Seminars in Immunology

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The type I membrane protein receptor carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) distinctively exhibits significant alternative splicing that allows for tunable functions upon homophilic binding. CEACAM1 is highly expressed in the tumor environment and is strictly regulated on lymphocytes such that its expression is restricted to activated cells where it is now recognized to function in tolerance pathways. CEACAM1 is also an important target for microbes which have co-opted these attributes of CEACAM1 for the purposes of invading the host and evading the immune system. These properties, among others, have focused attention on CEACAM1 as a unique target for immunotherapy in autoimmunity and cancer. This review examines recent structural information derived from the characterization of CEACAM1:CEACAM1 interactions and heterophilic modes of binding especially to microbes and how this relates to CEACAM1 function. Through this, we aim to provide insights into targeting CEACAM1 for therapeutic intervention.

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Section: Ceacam1 Igv Heterophilic Interactions With Host Ligands-thementioning

confidence: 99%

CEACAM1 structure and function in immunity and its therapeutic implications

Kim

Huang

Gandhi

et al. 2019

Seminars in Immunology

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“…This stimulates the Smad signalling pathway resulting in the upregulation of both fibronectin and integrin expression [9]. P1, an outer membrane protein in NTHi has been reported to be involved in CEACAM-1 and CEACAM-5 binding, thus facilitating adhesion and invasion of the nasopharynx and lower respiratory epithelium [38]. Similarly, CEACAM-1-engaging adhesins have also been identified in M. catarrhalis.…”

Section: Temporal Host Surface Receptor Upregulation In Different Bodmentioning

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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“…Members of this immunoglobulin (Ig) receptor family are expressed on the apical surface of mucosal cells lining the nasopharynx, the intestine, and the genitourinary tract [7,8]. Several gram-negative pathogens, including Haemophilus influenzae, H. aegyptius, Helicobacter pylori, Neisseria gonorrhoeae, N. meningitidis, and Moraxella catarrhalis, express specialized adhesins to associate with the amino-terminal Ig-variable (IgV)-like domain shared by all CEACAM family members [9][10][11][12][13]. Attachment to apically expressed CEACAMs appears to facilitate bacterial colonization of the mucosal surface, not only by providing a direct molecular connection to the epithelium, but also by suppressing the exfoliation and detachment of infected superficial cells [14][15][16].…”

Section: Introductionmentioning

confidence: 99%

“…A situation similar to N. gonorrhoeae Opa proteins has been observed for H. influenzae (Hinf) OMP P1, which functions as the CEACAM-binding adhesin of this microbe. OMP P1 proteins from a variety of Hinf isolates recognize CEACAM1, but at the same time do not bind to CEACAM3 [12]. The only CEACAMbinding OMP P1 variant that is recognized by CEACAM3 has been identified in the related species H. aegyptius [12].…”

Section: Introductionmentioning

confidence: 99%

“…OMP P1 proteins from a variety of Hinf isolates recognize CEACAM1, but at the same time do not bind to CEACAM3 [12]. The only CEACAMbinding OMP P1 variant that is recognized by CEACAM3 has been identified in the related species H. aegyptius [12]. Akin to neisserial Opa proteins, OMP P1 proteins isolated from different Haemophilus strains show a high degree of sequence variation in their extracellular parts [12].…”

Section: Introductionmentioning

confidence: 99%

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Adaptation to Host-Specific Bacterial Pathogens Drives Rapid Evolution of a Human Innate Immune Receptor

et al. 2019

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Graphical AbstractHighlights d The CEACAM3 gene appears recently in higher primates d It functions as a pathogen receptor and is one of the fastestevolving human genes d Human and chimp, but not gorilla or rhesus monkey, CEACAM3 binds human pathogens d CEACAM3 polymorphisms allow recognition of a broader set of bacterial pathogens SUMMARYThe selective pressure by infectious agents is a major driving force in the evolution of humans and other mammals. Members of the carcinoembryonic antigen-related cell adhesion molecule (CEACAM) family serve as receptors for bacterial pathogens of the genera Haemophilus, Helicobacter, Neisseria, and Moraxella, which engage CEACAMs via distinct surface adhesins. While microbial attachment to epithelial CEACAMs facilitates host colonization, recognition by CEACAM3, a phagocytic receptor expressed by granulocytes, eliminates CEACAMbinding bacteria. Sequence analysis of primate CEACAM3 orthologs reveals that this innate immune receptor is one of the most rapidly evolving human proteins. In particular, the pathogen-binding extracellular domain of CEACAM3 shows a high degree of non-synonymous versus synonymous nucleotide exchanges, indicating an exceptionally strong positive selection. Using CEACAM3 domains derived from different primates, we find that the amino acid alterations found in CEACAM3 translate into characteristic binding patterns for bacterial adhesins. One such amino acid residue is F62 in human and chimp CEACAM3, which is not present in other primates and which is critical for binding the OMP P1 adhesin of Haemophilus aegyptius. Incorporation of the F62containing motif into gorilla CEACAM3 results in a gain-of-function phenotype with regard to phagocytosis of H. aegyptius. Moreover, CEACAM3 polymorphisms found in human subpopulations widen the spectrum of recognized bacterial adhesins, suggesting an ongoing multivariate selection acting on this innate immune receptor. The species-specific detection of diverse bacterial adhesins helps to explain the exceptionally fast evolution of CEACAM3 within the primate lineage and provides an example of Red Queen dynamics in the human genome.

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Outer membrane protein P1 is the CEACAM‐binding adhesin of Haemophilus influenzae

Cited by 36 publications

References 45 publications

CEACAM1 structure and function in immunity and its therapeutic implications

CEACAM1 structure and function in immunity and its therapeutic implications

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

Adaptation to Host-Specific Bacterial Pathogens Drives Rapid Evolution of a Human Innate Immune Receptor

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