The Nontypeable <named-content content-type="genus-species">Haemophilus influenzae</named-content> Major Adhesin Hia Is a Dual-Function Lectin That Binds to Human-Specific Respiratory Tract Sialic Acid Glycan Receptors

ABSTRACT 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 pha...

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Autores principales:	John M. Atack, Christopher J. Day, Jessica Poole, Kenneth L. Brockman, Jamie R. L. Timms, Linda E. Winter, Thomas Haselhorst, Lauren O. Bakaletz, Stephen J. Barenkamp, Michael P. Jennings
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2020
Materias:	COPD NTHi adhesin autotransporter proteins bacterial pathogen glycan Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/b2682d6d2df04df69b1bd523da687501
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spelling	oai:doaj.org-article:b2682d6d2df04df69b1bd523da6875012021-11-15T15:55:43ZThe Nontypeable <named-content content-type="genus-species">Haemophilus influenzae</named-content> Major Adhesin Hia Is a Dual-Function Lectin That Binds to Human-Specific Respiratory Tract Sialic Acid Glycan Receptors10.1128/mBio.02714-202150-7511https://doaj.org/article/b2682d6d2df04df69b1bd523da6875012020-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02714-20https://doaj.org/toc/2150-7511ABSTRACT 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. IMPORTANCE Host-adapted bacterial pathogens like NTHi have evolved specific mechanisms to colonize their restricted host niche. Relatively few of the adhesins expressed by NTHi have been characterized as regards their binding affinity at the molecular level. In this work, we show that the major NTHi adhesin Hia preferentially binds to Neu5Ac-α2-6-sialyllactosamine, the form of sialic acid expressed in humans. The receptors targeted by Hia in the human airway mirror those targeted by influenza A virus and indicates the broad importance of sialic acid glycans as receptors for microbes that colonize the human airway.John M. AtackChristopher J. DayJessica PooleKenneth L. BrockmanJamie R. L. TimmsLinda E. WinterThomas HaselhorstLauren O. BakaletzStephen J. BarenkampMichael P. JenningsAmerican Society for MicrobiologyarticleCOPDNTHiadhesinautotransporter proteinsbacterial pathogenglycanMicrobiologyQR1-502ENmBio, Vol 11, Iss 6 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	COPD NTHi adhesin autotransporter proteins bacterial pathogen glycan Microbiology QR1-502
spellingShingle	COPD NTHi adhesin autotransporter proteins bacterial pathogen glycan Microbiology QR1-502 John M. Atack Christopher J. Day Jessica Poole Kenneth L. Brockman Jamie R. L. Timms Linda E. Winter Thomas Haselhorst Lauren O. Bakaletz Stephen J. Barenkamp Michael P. Jennings The Nontypeable <named-content content-type="genus-species">Haemophilus influenzae</named-content> Major Adhesin Hia Is a Dual-Function Lectin That Binds to Human-Specific Respiratory Tract Sialic Acid Glycan Receptors
description	ABSTRACT 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. IMPORTANCE Host-adapted bacterial pathogens like NTHi have evolved specific mechanisms to colonize their restricted host niche. Relatively few of the adhesins expressed by NTHi have been characterized as regards their binding affinity at the molecular level. In this work, we show that the major NTHi adhesin Hia preferentially binds to Neu5Ac-α2-6-sialyllactosamine, the form of sialic acid expressed in humans. The receptors targeted by Hia in the human airway mirror those targeted by influenza A virus and indicates the broad importance of sialic acid glycans as receptors for microbes that colonize the human airway.
format	article
author	John M. Atack Christopher J. Day Jessica Poole Kenneth L. Brockman Jamie R. L. Timms Linda E. Winter Thomas Haselhorst Lauren O. Bakaletz Stephen J. Barenkamp Michael P. Jennings
author_facet	John M. Atack Christopher J. Day Jessica Poole Kenneth L. Brockman Jamie R. L. Timms Linda E. Winter Thomas Haselhorst Lauren O. Bakaletz Stephen J. Barenkamp Michael P. Jennings
author_sort	John M. Atack
title	The Nontypeable <named-content content-type="genus-species">Haemophilus influenzae</named-content> Major Adhesin Hia Is a Dual-Function Lectin That Binds to Human-Specific Respiratory Tract Sialic Acid Glycan Receptors
title_short	The Nontypeable <named-content content-type="genus-species">Haemophilus influenzae</named-content> Major Adhesin Hia Is a Dual-Function Lectin That Binds to Human-Specific Respiratory Tract Sialic Acid Glycan Receptors
title_full	The Nontypeable <named-content content-type="genus-species">Haemophilus influenzae</named-content> Major Adhesin Hia Is a Dual-Function Lectin That Binds to Human-Specific Respiratory Tract Sialic Acid Glycan Receptors
title_fullStr	The Nontypeable <named-content content-type="genus-species">Haemophilus influenzae</named-content> Major Adhesin Hia Is a Dual-Function Lectin That Binds to Human-Specific Respiratory Tract Sialic Acid Glycan Receptors
title_full_unstemmed	The Nontypeable <named-content content-type="genus-species">Haemophilus influenzae</named-content> Major Adhesin Hia Is a Dual-Function Lectin That Binds to Human-Specific Respiratory Tract Sialic Acid Glycan Receptors
title_sort	nontypeable <named-content content-type="genus-species">haemophilus influenzae</named-content> major adhesin hia is a dual-function lectin that binds to human-specific respiratory tract sialic acid glycan receptors
publisher	American Society for Microbiology
publishDate	2020
url	https://doaj.org/article/b2682d6d2df04df69b1bd523da687501
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The Nontypeable <named-content content-type="genus-species">Haemophilus influenzae</named-content> Major Adhesin Hia Is a Dual-Function Lectin That Binds to Human-Specific Respiratory Tract Sialic Acid Glycan Receptors

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