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The Nontypeable Haemophilus influenzae Major Adhesin Hia Is a Dual-Function Lectin That Binds to Human-Specific Respiratory Tract Sialic Acid Glycan Receptors

NTHi is a human-adapted pathogen that colonizes the human respiratory tract. Strains of NTHi express multiple adhesins; however, there is a unique, mutually exclusive relationship between the major adhesins Hia and HMW1 and HMW2 (HMW1/2). Approximately 25% of NTHi strains express Hia, a phase-variab...

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Autores principales: Atack, John M., Day, Christopher J., Poole, Jessica, Brockman, Kenneth L., Timms, Jamie R. L., Winter, Linda E., Haselhorst, Thomas, Bakaletz, Lauren O., Barenkamp, Stephen J., Jennings, Michael P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642680/
https://www.ncbi.nlm.nih.gov/pubmed/33144377
http://dx.doi.org/10.1128/mBio.02714-20
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author Atack, John M.
Day, Christopher J.
Poole, Jessica
Brockman, Kenneth L.
Timms, Jamie R. L.
Winter, Linda E.
Haselhorst, Thomas
Bakaletz, Lauren O.
Barenkamp, Stephen J.
Jennings, Michael P.
author_facet Atack, John M.
Day, Christopher J.
Poole, Jessica
Brockman, Kenneth L.
Timms, Jamie R. L.
Winter, Linda E.
Haselhorst, Thomas
Bakaletz, Lauren O.
Barenkamp, Stephen J.
Jennings, Michael P.
author_sort Atack, John M.
collection PubMed
description NTHi is a human-adapted pathogen that colonizes the human respiratory tract. Strains of NTHi express multiple adhesins; however, there is a unique, mutually exclusive relationship between the major adhesins Hia and HMW1 and HMW2 (HMW1/2). Approximately 25% of NTHi strains express Hia, a phase-variable autotransporter protein that has a critical role in colonization of the host nasopharynx. The remaining 75% of strains express HMW1/2. Previous work has shown that the HMW1 and HMW2 proteins mediate binding to 2-3- and 2-6-linked sialic acid glycans found in the human respiratory tract. Here, we show that the high-affinity binding domain of Hia, binding domain 1 (BD1), is responsible for binding to α2-6-sialyllactosamine (2-6 SLN) glycans. BD1 is highly specific for glycans that incorporate the form of sialic acid expressed by humans, N-acetylneuraminic acid (Neu5Ac). We further show that Hia has lower-affinity binding activity for 2-3-linked sialic acid and that this binding activity is mediated via a distinct domain. Thus, Hia with its dual binding activities functionally mimics the combined activities of the HMW1 and HMW2 adhesins. In addition, we show that Hia has a role in biofilm formation by strains of NTHi that express the adhesin. Knowledge of the binding affinity of this major NTHi adhesin and putative vaccine candidate will direct and inform development of future vaccines and therapeutic strategies for this important pathogen.
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spelling pubmed-76426802020-11-17 The Nontypeable Haemophilus influenzae Major Adhesin Hia Is a Dual-Function Lectin That Binds to Human-Specific Respiratory Tract Sialic Acid Glycan Receptors Atack, John M. Day, Christopher J. Poole, Jessica Brockman, Kenneth L. Timms, Jamie R. L. Winter, Linda E. Haselhorst, Thomas Bakaletz, Lauren O. Barenkamp, Stephen J. Jennings, Michael P. mBio Research Article NTHi is a human-adapted pathogen that colonizes the human respiratory tract. Strains of NTHi express multiple adhesins; however, there is a unique, mutually exclusive relationship between the major adhesins Hia and HMW1 and HMW2 (HMW1/2). Approximately 25% of NTHi strains express Hia, a phase-variable autotransporter protein that has a critical role in colonization of the host nasopharynx. The remaining 75% of strains express HMW1/2. Previous work has shown that the HMW1 and HMW2 proteins mediate binding to 2-3- and 2-6-linked sialic acid glycans found in the human respiratory tract. Here, we show that the high-affinity binding domain of Hia, binding domain 1 (BD1), is responsible for binding to α2-6-sialyllactosamine (2-6 SLN) glycans. BD1 is highly specific for glycans that incorporate the form of sialic acid expressed by humans, N-acetylneuraminic acid (Neu5Ac). We further show that Hia has lower-affinity binding activity for 2-3-linked sialic acid and that this binding activity is mediated via a distinct domain. Thus, Hia with its dual binding activities functionally mimics the combined activities of the HMW1 and HMW2 adhesins. In addition, we show that Hia has a role in biofilm formation by strains of NTHi that express the adhesin. Knowledge of the binding affinity of this major NTHi adhesin and putative vaccine candidate will direct and inform development of future vaccines and therapeutic strategies for this important pathogen. American Society for Microbiology 2020-11-03 /pmc/articles/PMC7642680/ /pubmed/33144377 http://dx.doi.org/10.1128/mBio.02714-20 Text en Copyright © 2020 Atack et al. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Atack, John M.
Day, Christopher J.
Poole, Jessica
Brockman, Kenneth L.
Timms, Jamie R. L.
Winter, Linda E.
Haselhorst, Thomas
Bakaletz, Lauren O.
Barenkamp, Stephen J.
Jennings, Michael P.
The Nontypeable Haemophilus influenzae Major Adhesin Hia Is a Dual-Function Lectin That Binds to Human-Specific Respiratory Tract Sialic Acid Glycan Receptors
title The Nontypeable Haemophilus influenzae Major Adhesin Hia Is a Dual-Function Lectin That Binds to Human-Specific Respiratory Tract Sialic Acid Glycan Receptors
title_full The Nontypeable Haemophilus influenzae Major Adhesin Hia Is a Dual-Function Lectin That Binds to Human-Specific Respiratory Tract Sialic Acid Glycan Receptors
title_fullStr The Nontypeable Haemophilus influenzae Major Adhesin Hia Is a Dual-Function Lectin That Binds to Human-Specific Respiratory Tract Sialic Acid Glycan Receptors
title_full_unstemmed The Nontypeable Haemophilus influenzae Major Adhesin Hia Is a Dual-Function Lectin That Binds to Human-Specific Respiratory Tract Sialic Acid Glycan Receptors
title_short The Nontypeable Haemophilus influenzae Major Adhesin Hia Is a Dual-Function Lectin That Binds to Human-Specific Respiratory Tract Sialic Acid Glycan Receptors
title_sort nontypeable haemophilus influenzae major adhesin hia is a dual-function lectin that binds to human-specific respiratory tract sialic acid glycan receptors
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642680/
https://www.ncbi.nlm.nih.gov/pubmed/33144377
http://dx.doi.org/10.1128/mBio.02714-20
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