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...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2020-12-01
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| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mBio.02714-20 |
| _version_ | 1818822612929740800 |
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| 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 |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-18T23:26:52Z |
| format | Article |
| id | doaj.art-b2682d6d2df04df69b1bd523da687501 |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-12-18T23:26:52Z |
| publishDate | 2020-12-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-b2682d6d2df04df69b1bd523da6875012022-12-21T20:47:45ZengAmerican Society for MicrobiologymBio2150-75112020-12-0111610.1128/mBio.02714-20The 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 ReceptorsJohn M. Atack0Christopher J. Day1Jessica Poole2Kenneth L. Brockman3Jamie R. L. Timms4Linda E. Winter5Thomas Haselhorst6Lauren O. Bakaletz7Stephen J. Barenkamp8Michael P. Jennings9Institute for Glycomics, Griffith University, Gold Coast, Queensland, AustraliaInstitute for Glycomics, Griffith University, Gold Coast, Queensland, AustraliaInstitute for Glycomics, Griffith University, Gold Coast, Queensland, AustraliaCenter for Microbial Pathogenesis, The Research Institute at Nationwide Children’s Hospital and The Ohio State University College of Medicine, Columbus, Ohio, USAInstitute for Glycomics, Griffith University, Gold Coast, Queensland, AustraliaDepartment of Pediatrics, Saint Louis University School of Medicine, and the Pediatric Research Institute, Cardinal Glennon Children’s Medical Center, Saint Louis, Missouri, USAInstitute for Glycomics, Griffith University, Gold Coast, Queensland, AustraliaCenter for Microbial Pathogenesis, The Research Institute at Nationwide Children’s Hospital and The Ohio State University College of Medicine, Columbus, Ohio, USADepartment of Pediatrics, Saint Louis University School of Medicine, and the Pediatric Research Institute, Cardinal Glennon Children’s Medical Center, Saint Louis, Missouri, USAInstitute for Glycomics, Griffith University, Gold Coast, Queensland, AustraliaABSTRACT 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.https://journals.asm.org/doi/10.1128/mBio.02714-20COPDNTHiadhesinautotransporter proteinsbacterial pathogenglycan |
| spellingShingle | 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 mBio COPD NTHi adhesin autotransporter proteins bacterial pathogen glycan |
| 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_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_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_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 |
| topic | COPD NTHi adhesin autotransporter proteins bacterial pathogen glycan |
| url | https://journals.asm.org/doi/10.1128/mBio.02714-20 |
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