Haemophilus influenzae stores and distributes hemin by using Protein E

Jubair, Tamim Al; Singh, Birendra; Fleury, Christophe; Blom, Anna M.; Mörgelin, Matthias; Thunnissen, Marjolein M.G.M.; Riesbeck, Kristian

doi:10.1016/j.ijmm.2014.04.015

Cited by 5 publications

(15 citation statements)

References 45 publications

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“…While a variety of heme storage, transfer, and degradation properties have been assigned to these proteins, their involvement in resisting heme toxicity is clear. Additionally, non-HemS family proteins have been found to bind heme and play a role in heme homeostasis, including the small outer-membrane Protein E of H. influenzae and the Cu,Zn superoxide dismutase of Haemophilus ducreyi [245,246]. …”

Section: Heme Toxicity and Tolerancementioning

confidence: 99%

Heme Synthesis and Acquisition in Bacterial Pathogens

Choby

Skaar

2016

Journal of Molecular Biology

256

266

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Bacterial pathogens require the iron-containing cofactor heme to cause disease. Heme is essential to the function of hemoproteins, which are involved in energy generation by the electron transport chain, detoxification of host immune effectors, and other processes. During infection, bacterial pathogens must synthesize heme or acquire heme from the host; however, host heme is sequestered in high-affinity hemoproteins. Pathogens have evolved elaborate strategies to acquire heme from host sources, particularly hemoglobin, and both heme acquisition and synthesis are important for pathogenesis. Paradoxically, excess heme is toxic to bacteria and pathogens must rely on heme detoxification strategies. Heme is a key nutrient in the struggle for survival between host and pathogen, and its study has offered significant insight into the molecular mechanisms of bacterial pathogenesis.

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Section: Heme Toxicity and Tolerancementioning

confidence: 99%

Heme Synthesis and Acquisition in Bacterial Pathogens

Choby

Skaar

2016

Journal of Molecular Biology

256

266

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“…SapF is also capable of regulating heme transport and storage, as well as transporting other solutes important for maintaining an infectious phenotype . The vaccine candidate protein E, already defined as an adhesin of NTHi, can also bind hemin . A binding pocket within protein E is able to act as a storage site for hemin, allowing its later distribution to nearby NTHi that are starved of it .…”

Section: Sequestration Of Key Metabolic Ions and Nutrientsmentioning

confidence: 99%

“…The vaccine candidate protein E, already defined as an adhesin of NTHi, can also bind hemin . A binding pocket within protein E is able to act as a storage site for hemin, allowing its later distribution to nearby NTHi that are starved of it . While the import and usage of Fe remains paramount in the hierarchy of transition metals, others are relevant to the nutrition of NTHi to support survival during colonization and infection.…”

Section: Sequestration Of Key Metabolic Ions and Nutrientsmentioning

confidence: 99%

Host–pathogen interactions of nontypeable Haemophilus influenzae: from commensal to pathogen

2016

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Nontypeable Haemophilus influenzae (NTHi) is a commensal microbe often isolated from the upper and lower respiratory tract. This bacterial species can cause sinusitis, acute otitis media in preschool children, exacerbations in patients suffering from chronic obstructive pulmonary disease, as well as conjunctivitis and bacteremia. Since the introduction of a vaccine against H. influenzae serotype b in the 1990s, the burden of H. influenzae‐related infections has been increasingly dominated by NTHi. Understanding the ability of NTHi to cause infection is currently an expanding area of study. NTHi is able to exert differential binding to the host tissue through the use of a broad range of adhesins. NTHi survival in the host is multifaceted, that is, using virulence factors involved in complement resistance, biofilm, modified immunoglobulin responses, and, finally, formation and utilization of host proteins as a secondary strategy of increasing the adhesive ability.

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“…Ligands, recombinant purified PH, or other bacterial proteins PE (20,22) and UHP_09011 (17) (50 nM) were immobilized overnight on Polysorb microtitre plates (Nunc-Immuno; Nunc, Roskilde, Denmark) in Tris-HCl (pH 9.0) for 15 h at 4˚C. After washing, His-tagged PH or Vn fragments as outlined in Fig.…”

Section: Elisamentioning

confidence: 99%

“…H. influenzae PE and UPH_09011 were included for comparison as positive and negative controls, respectively (16,17,22). Recombinant proteins were coated in microtiter plates, followed by addition of Vn at increasing concentrations.…”

Section: Ph Has a High Affinity For Vn And Simultaneously Interacts Wmentioning

confidence: 99%

Haemophilus influenzae Type f Hijacks Vitronectin Using Protein H To Resist Host Innate Immunity and Adhere to Pulmonary Epithelial Cells

Al-Jubair

Mukherjee

Oosterhuis

et al. 2015

The Journal of Immunology

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The incidence of invasive Haemophilus influenzae type b (Hib) disease has significantly decreased since the introduction of an efficient vaccine against Hib. However, in contrast to Hib, infections caused by H. influenzae serotype f (Hif) are emerging. We recently did a whole genome sequencing of an invasive Hif isolate, and reported that Hif interacts with factor H by expressing protein H (PH). In this study, upon screening with various human complement regulators, we revealed that PH is also a receptor for vitronectin (Vn), an abundant plasma protein that regulates the terminal pathway of the human complement system in addition to being a component of the extracellular matrix. Bacterial Vn binding was significantly reduced when the lph gene encoding PH was deleted in an invasive Hif isolate. The dissociation constant (KD) of the interaction between recombinant PH and Vn was 2.2 μM, as revealed by Biolayer interferometry. We found that PH has different regions for simultaneous interaction with both Vn and factor H, and that it recognized the C-terminal part of Vn (aa 352–362). Importantly, PH-dependent Vn binding resulted in better survival of the wild-type Hif or PH-expressing Escherichia coli when exposed to human serum. Finally, we observed that PH mediated an increased bacterial adherence to alveolar epithelial cells in the presence of Vn. In conclusion, our study reveals that PH most likely plays an important role in Hif pathogenesis by increasing serum resistance and adhesion to the airways.

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Haemophilus influenzae stores and distributes hemin by using Protein E

Cited by 5 publications

References 45 publications

Heme Synthesis and Acquisition in Bacterial Pathogens

Heme Synthesis and Acquisition in Bacterial Pathogens

Host–pathogen interactions of nontypeable Haemophilus influenzae: from commensal to pathogen

Haemophilus influenzae Type f Hijacks Vitronectin Using Protein H To Resist Host Innate Immunity and Adhere to Pulmonary Epithelial Cells

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