Nontypeable<i>Haemophilus influenzae</i>Adhesin Protein E: Characterization and Biological Activity

Ronander, Elena; Brant, Marta; Eriksson, Emily M.; Mörgelin, Matthias; Hällgren, Oskar; Westergren‐Thorsson, Gunilla; Forsgren, Arne; Riesbeck, Kristian

doi:10.1086/596211

Cited by 44 publications

(53 citation statements)

References 32 publications

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“…Flow cytometry analysis with an affinitypurified anti-PE pAb confirmed that the H. influenzae PE mutant (NTHi 3655⌬pe) was PE deficient (Fig. 2D) (20). Moreover, a pAb against human vitronectin inhibited the binding of vitronectin to NTHi 3655 as examined in a direct binding assay (Fig.…”

Section: Pe From H Influenzae Binds Human Vitronectinmentioning

confidence: 66%

“…A relatively large area of PE (aa 41-108) is involved in binding to vitronectin. However, the highest signal in the ELISA analysis was obtained with the peptide comprising PE(84 -108), which includes the adhesive domain mediating attachment to epithelial cells (20,21). PE(84 -108) has been shown to have affinity for the lung carcinoma cell line A549, the conjunctival epithelial cell line Chang, and the pharynx-derived cell line Detroit.…”

Section: Discussionmentioning

confidence: 99%

“…The recently discovered H. influenzae protein E (PE) is a lowmolecular-mass (16 kDa) outer membrane lipoprotein with adhesive properties (20,21). PE-expressing H. influenzae in addition to soluble recombinant PE(22-160) without a lipid moiety induces a proinflammatory epithelial cell response, resulting in an increased IL-8 secretion and ICAM-1 up-regulation that leads to an enhanced neutrophil adherence to epithelial cells.…”

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confidence: 99%

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NontypeableHaemophilus influenzaeProtein E Binds Vitronectin and Is Important for Serum Resistance

Hallström

Blom

Zipfel

et al. 2009

The Journal of Immunology

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138

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Nontypeable Haemophilus influenzae (NTHi) commonly causes local disease in the upper and lower respiratory tract and has recently been shown to interfere with both the classical and alternative pathways of complement activation. The terminal pathway of the complement system is regulated by vitronectin that is a component of both plasma and the extracellular matrix. In this study, we identify protein E (PE; 16 kDa), which is a recently characterized ubiquitous outer membrane protein, as a vitronectin-binding protein of NTHi. A PE-deficient NTHi mutant had a markedly reduced survival in serum compared with the PE-expressing isogenic NTHi wild type. Moreover, the PE-deficient mutant showed a significantly decreased binding to both soluble and immobilized vitronectin. In parallel, PE-expressing Escherichia coli bound soluble vitronectin and adhered to immobilized vitronectin compared with controls. Surface plasmon resonance technology revealed a KD of 0.4 μΜ for the interaction between recombinant PE and immobilized vitronectin. Moreover, the PE-dependent vitronectin-binding site was located at the heparin-binding domains of vitronectin and the major vitronectin-binding domain was found in the central core of PE (aa 84–108). Importantly, vitronectin bound to the surface of NTHi 3655 reduced membrane attack complex-induced hemolysis. In contrast to incubation with normal human serum, NTHi 3655 showed a reduced survival in vitronectin-depleted human serum, thus demonstrating that vitronectin mediates a protective role at the bacterial surface. Our findings show that PE, by binding vitronectin, may play an important role in NTHi pathogenesis.

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Section: Pe From H Influenzae Binds Human Vitronectinmentioning

confidence: 66%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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NontypeableHaemophilus influenzaeProtein E Binds Vitronectin and Is Important for Serum Resistance

Hallström

Blom

Zipfel

et al. 2009

The Journal of Immunology

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138

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“…influenzae protein E (PE) is a 16 kDa, highly conserved (96.9%-100%), ubiquitous outer membrane lipoprotein that exists in both encapsulated H. influenzae and NTHi (Singh et al, 2010). PE was initially described as an adhesin that binds to epithelial cells of different origins including those from COPD patients (Ronander et al, 2009). In addition, PE simultaneously binds to extracellular matrix proteins and plasminogen, interactions that all contribute to bacterial virulence (Barthel et al, 2012;Hallstrom et al, 2009;Hallstrom et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Haemophilus influenzae stores and distributes hemin by using Protein E

Jubair

Singh

Fleury

et al. 2014

International Journal of Medical Microbiology

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“…PE uses the central 24-aa-long core domain (i.e., aa 84-108) to contact human epithelial cells and to induce proinflammatory responses. PE also binds human vitronectin, an ECM component, adhesion protein and terminal complement regulator (22).…”

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confidence: 99%

Haemophilus influenzae Uses the Surface Protein E To Acquire Human Plasminogen and To Evade Innate Immunity

Barthel

Singh

Riesbeck

et al. 2012

The Journal of Immunology

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Pathogenic microbes acquire the human plasma protein plasminogen to their surface. In this article, we characterize binding of this important coagulation regulator to the respiratory pathogen nontypeable Haemophilus influenzae and identify the Haemophilus surface protein E (PE) as a new plasminogen-binding protein. Plasminogen binds dose dependently to intact bacteria and to purified PE. The plasminogen–PE interaction is mediated by lysine residues and is also affected by ionic strength. The H. influenzae PE knockout strain (nontypeable H. influenzae 3655Δpe) bound plasminogen with ∼65% lower intensity as compared with the wild-type, PE-expressing strain. In addition, PE expressed ectopically on the surface of Escherichia coli also bound plasminogen. Plasminogen, either attached to intact H. influenzae or bound to PE, was accessible for urokinase plasminogen activator. The converted active plasmin cleaved the synthetic substrate S-2251, and the natural substrates fibrinogen and C3b. Using synthetic peptides that cover the complete sequence of the PE protein, the major plasminogen-binding region was localized to a linear 28-aa-long N-terminal peptide, which represents aa 41–68. PE binds plasminogen and also vitronectin, and the two human plasma proteins compete for PE binding. Thus, PE is a major plasminogen-binding protein of the Gram-negative bacterium H. influenzae, and when converted to plasmin, PE-bound plasmin aids in immune evasion and contributes to bacterial virulence.

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NontypeableHaemophilus influenzaeAdhesin Protein E: Characterization and Biological Activity

Cited by 44 publications

References 32 publications

NontypeableHaemophilus influenzaeProtein E Binds Vitronectin and Is Important for Serum Resistance

NontypeableHaemophilus influenzaeProtein E Binds Vitronectin and Is Important for Serum Resistance

Haemophilus influenzae stores and distributes hemin by using Protein E

Haemophilus influenzae Uses the Surface Protein E To Acquire Human Plasminogen and To Evade Innate Immunity

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