MORAXELLA CATARRHALIS OUTER MEMBRANE PROTEINS AND THEIR INTERACTIONS WITH THE HUMAN HOST

Thuan Tong Tan

MORAXELLA CATARRHALIS OUTER MEMBRANE PROTEINS AND THEIR INTERACTIONS WITH THE HUMAN HOST

Thuan Tong Tan

Klinisk mikrobiologi, Malmö

Forskningsoutput: Avhandling › Doktorsavhandling (sammanläggning)

Sammanfattning

Moraxella catarrhalis is an airway pathogen whose role in infection has been increasingly recognized in recent years. Most authorities in this field now agree that M. catarrhalis causes significant morbidity and is not just a harmless commensal. The universal prevalence of BRO ?-lactamases in this pathogen is a serious concern. In addition, M. catarrhalis may be further propelled into a more prominent position in the hierarchy of respiratory infectious agents due to the phenomenon of ?non-vaccine type replacement? as a result of the wider usage of vaccines against other pathogens in the same ecological niche, such as Haemophilus influenzae and Streptococcus pneumoniae.

There is currently no available vaccine against M. catarrhalis. A detailed analysis of the interactions of this bacterium with the human host is necessary to identify ways to interfere with its colonization and infection. To this end, we have focused on the interactions via three outer membrane proteins, namely UspA1 (ubiquitous surface protein A1), UspA2 and MID (Moraxella catarrhalis IgD binding protein). We found that UspA1 and A2 could bind fibronectin and laminin, and characterized these interactions. We also detailed a novel interaction of UspA1 and A2 with the complement protein C3. The UspA1/A2-dependent C3 binding contributes to its serum resistant phenotype and is a way in which M. catarrhalis combat the innate immunity. Furthermore, we showed that this interaction could contribute to the survival of copathogens. An analysis of naturally acquired serological responses to these two proteins and those of MID showed that the functional domains identified here (fibronectin binding region in UspA1299-452 and UspA2165-318, C3 binding region in UspA2) and those identified in other studies (CEACAM binding region of UspA1, the MID764-913 adhesive domain) evoked significant immune responses. The better understanding of the interactions and the identification of important domains in these three proteins represent significant advances in the quest for a suitable vaccine against M. catarrhalis.

Originalspråk	engelska
Kvalifikation	Doktor
Tilldelande institution	Klinisk mikrobiologi, Malmö
Handledare	Riesbeck, Kristian, handledare
Tilldelningsdatum	2007 jan. 19
Förlag	Medical Microbiology, Lund University
ISBN (tryckt)	91-85559-77-6
Status	Published - 2007

Bibliografisk information

Defence details

Date: 2007-01-19
Time: 14:00
Place: Patologiska Institutionens föreläsningssal, Ingång 78, Universitetssjukhuset MAS, Malmö

External reviewer(s)

Name: Høiby, Niels
Title: Professor
Affiliation: Department of Bacteriology, Institute of Medical Microbiology and Immunology, University of Copenhag

---

<div class="article_info">T.T. Tan, T Nordström, A Forsgren and K Riesbeck. <span class="article_issue_date">2005</span>. <span class="article_title">The respiratory pathogen Moraxella catarrhalis adheres to epithelial cells by interacting with fibronectin through ubiquitous surface proteins A1 and A2.</span> <span class="journal_series_title">The Journal of Infectious Diseases</span>, <span class="journal_volume">vol 192</span> <span class="journal_pages">pp 1029-38</span>.</div>
<div class="article_info">T.T. Tan, A Forsgren and K Riesbeck. <span class="article_issue_date">2006</span>. <span class="article_title">The respiratory pathogen Moraxella catarrhalis binds to laminin via ubiquitous surface proteins A1 and A2.</span> <span class="journal_series_title">The Journal of Infectious Diseases</span>, <span class="journal_volume">vol 194</span> <span class="journal_pages">pp 493-7</span>.</div>
<div class="article_info">T Nordström, A Blom, A.M. Blom, T.T. Tan, A Forsgren and K Riesbeck. <span class="article_issue_date">2005</span>. <span class="article_title">Ionic binding of C3 to the human pathogen Moraxella catarrhalis is a unique mechanism for combating innate immunity.</span> <span class="journal_series_title">The Journal of Infectious Diseases</span>, <span class="journal_volume">vol 175</span> <span class="journal_pages">pp 3628-26</span>.</div>
<div class="article_info">T.T. Tan, M Mörgelin, A Forsgren and K Riesbeck. <span class="article_issue_date">2006</span>. <span class="article_title">Haemophilus influenzae survival during complement-mediated attacks is promoted by Moraxella catarrhalis outer membrane vesicles.</span> <span class="journal_series_title">The Journal of Infectious Diseases</span>, (submitted)</div>
<div class="article_info">T.T. Tan, J.J. Christensen, M.H. Dziegiel, A Forsgren and K Riesbeck. <span class="article_issue_date">2006</span>. <span class="article_title">Comparison of the serological responses to Moraxella catarrhalis immunoglobulin D–binding outer membrane protein and the ubiquitous surface proteins A1 and A2.</span> <span class="journal_series_title">Infection and Immunity</span>, <span class="journal_volume">vol 74</span> <span class="journal_pages">pp 6377-86</span>.</div>

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title = "MORAXELLA CATARRHALIS OUTER MEMBRANE PROTEINS AND THEIR INTERACTIONS WITH THE HUMAN HOST",

abstract = "Moraxella catarrhalis is an airway pathogen whose role in infection has been increasingly recognized in recent years. Most authorities in this field now agree that M. catarrhalis causes significant morbidity and is not just a harmless commensal. The universal prevalence of BRO ?-lactamases in this pathogen is a serious concern. In addition, M. catarrhalis may be further propelled into a more prominent position in the hierarchy of respiratory infectious agents due to the phenomenon of ?non-vaccine type replacement? as a result of the wider usage of vaccines against other pathogens in the same ecological niche, such as Haemophilus influenzae and Streptococcus pneumoniae. There is currently no available vaccine against M. catarrhalis. A detailed analysis of the interactions of this bacterium with the human host is necessary to identify ways to interfere with its colonization and infection. To this end, we have focused on the interactions via three outer membrane proteins, namely UspA1 (ubiquitous surface protein A1), UspA2 and MID (Moraxella catarrhalis IgD binding protein). We found that UspA1 and A2 could bind fibronectin and laminin, and characterized these interactions. We also detailed a novel interaction of UspA1 and A2 with the complement protein C3. The UspA1/A2-dependent C3 binding contributes to its serum resistant phenotype and is a way in which M. catarrhalis combat the innate immunity. Furthermore, we showed that this interaction could contribute to the survival of copathogens. An analysis of naturally acquired serological responses to these two proteins and those of MID showed that the functional domains identified here (fibronectin binding region in UspA1299-452 and UspA2165-318, C3 binding region in UspA2) and those identified in other studies (CEACAM binding region of UspA1, the MID764-913 adhesive domain) evoked significant immune responses. The better understanding of the interactions and the identification of important domains in these three proteins represent significant advances in the quest for a suitable vaccine against M. catarrhalis.",

keywords = "Mikrobiologi, bakteriologi, virologi, mykologi, virology, mycology, Microbiology, bacteriology, MID, UspA1, UspA2",

author = "Tan, {Thuan Tong}",

note = "Defence details Date: 2007-01-19 Time: 14:00 Place: Patologiska Institutionens f{\"o}rel{\"a}sningssal, Ing{\aa}ng 78, Universitetssjukhuset MAS, Malm{\"o} External reviewer(s) Name: H{\o}iby, Niels Title: Professor Affiliation: Department of Bacteriology, Institute of Medical Microbiology and Immunology, University of Copenhag --- <div class={"}article_info{"}>T.T. Tan, T Nordstr{\"o}m, A Forsgren and K Riesbeck. <span class={"}article_issue_date{"}>2005</span>. <span class={"}article_title{"}>The respiratory pathogen Moraxella catarrhalis adheres to epithelial cells by interacting with fibronectin through ubiquitous surface proteins A1 and A2.</span> <span class={"}journal_series_title{"}>The Journal of Infectious Diseases</span>, <span class={"}journal_volume{"}>vol 192</span> <span class={"}journal_pages{"}>pp 1029-38</span>.</div> <div class={"}article_info{"}>T.T. Tan, A Forsgren and K Riesbeck. <span class={"}article_issue_date{"}>2006</span>. <span class={"}article_title{"}>The respiratory pathogen Moraxella catarrhalis binds to laminin via ubiquitous surface proteins A1 and A2.</span> <span class={"}journal_series_title{"}>The Journal of Infectious Diseases</span>, <span class={"}journal_volume{"}>vol 194</span> <span class={"}journal_pages{"}>pp 493-7</span>.</div> <div class={"}article_info{"}>T Nordstr{\"o}m, A Blom, A.M. Blom, T.T. Tan, A Forsgren and K Riesbeck. <span class={"}article_issue_date{"}>2005</span>. <span class={"}article_title{"}>Ionic binding of C3 to the human pathogen Moraxella catarrhalis is a unique mechanism for combating innate immunity.</span> <span class={"}journal_series_title{"}>The Journal of Infectious Diseases</span>, <span class={"}journal_volume{"}>vol 175</span> <span class={"}journal_pages{"}>pp 3628-26</span>.</div> <div class={"}article_info{"}>T.T. Tan, M M{\"o}rgelin, A Forsgren and K Riesbeck. <span class={"}article_issue_date{"}>2006</span>. <span class={"}article_title{"}>Haemophilus influenzae survival during complement-mediated attacks is promoted by Moraxella catarrhalis outer membrane vesicles.</span> <span class={"}journal_series_title{"}>The Journal of Infectious Diseases</span>, (submitted)</div> <div class={"}article_info{"}>T.T. Tan, J.J. Christensen, M.H. Dziegiel, A Forsgren and K Riesbeck. <span class={"}article_issue_date{"}>2006</span>. <span class={"}article_title{"}>Comparison of the serological responses to Moraxella catarrhalis immunoglobulin D–binding outer membrane protein and the ubiquitous surface proteins A1 and A2.</span> <span class={"}journal_series_title{"}>Infection and Immunity</span>, <span class={"}journal_volume{"}>vol 74</span> <span class={"}journal_pages{"}>pp 6377-86</span>.</div>",

year = "2007",

language = "English",

isbn = "91-85559-77-6",

publisher = "Medical Microbiology, Lund University",

type = "Doctoral Thesis (compilation)",

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}

TY - THES

T1 - MORAXELLA CATARRHALIS OUTER MEMBRANE PROTEINS AND THEIR INTERACTIONS WITH THE HUMAN HOST

AU - Tan, Thuan Tong

N1 - Defence details Date: 2007-01-19 Time: 14:00 Place: Patologiska Institutionens föreläsningssal, Ingång 78, Universitetssjukhuset MAS, Malmö External reviewer(s) Name: Høiby, Niels Title: Professor Affiliation: Department of Bacteriology, Institute of Medical Microbiology and Immunology, University of Copenhag --- <div class="article_info">T.T. Tan, T Nordström, A Forsgren and K Riesbeck. <span class="article_issue_date">2005</span>. <span class="article_title">The respiratory pathogen Moraxella catarrhalis adheres to epithelial cells by interacting with fibronectin through ubiquitous surface proteins A1 and A2.</span> <span class="journal_series_title">The Journal of Infectious Diseases</span>, <span class="journal_volume">vol 192</span> <span class="journal_pages">pp 1029-38</span>.</div> <div class="article_info">T.T. Tan, A Forsgren and K Riesbeck. <span class="article_issue_date">2006</span>. <span class="article_title">The respiratory pathogen Moraxella catarrhalis binds to laminin via ubiquitous surface proteins A1 and A2.</span> <span class="journal_series_title">The Journal of Infectious Diseases</span>, <span class="journal_volume">vol 194</span> <span class="journal_pages">pp 493-7</span>.</div> <div class="article_info">T Nordström, A Blom, A.M. Blom, T.T. Tan, A Forsgren and K Riesbeck. <span class="article_issue_date">2005</span>. <span class="article_title">Ionic binding of C3 to the human pathogen Moraxella catarrhalis is a unique mechanism for combating innate immunity.</span> <span class="journal_series_title">The Journal of Infectious Diseases</span>, <span class="journal_volume">vol 175</span> <span class="journal_pages">pp 3628-26</span>.</div> <div class="article_info">T.T. Tan, M Mörgelin, A Forsgren and K Riesbeck. <span class="article_issue_date">2006</span>. <span class="article_title">Haemophilus influenzae survival during complement-mediated attacks is promoted by Moraxella catarrhalis outer membrane vesicles.</span> <span class="journal_series_title">The Journal of Infectious Diseases</span>, (submitted)</div> <div class="article_info">T.T. Tan, J.J. Christensen, M.H. Dziegiel, A Forsgren and K Riesbeck. <span class="article_issue_date">2006</span>. <span class="article_title">Comparison of the serological responses to Moraxella catarrhalis immunoglobulin D–binding outer membrane protein and the ubiquitous surface proteins A1 and A2.</span> <span class="journal_series_title">Infection and Immunity</span>, <span class="journal_volume">vol 74</span> <span class="journal_pages">pp 6377-86</span>.</div>

PY - 2007

Y1 - 2007

N2 - Moraxella catarrhalis is an airway pathogen whose role in infection has been increasingly recognized in recent years. Most authorities in this field now agree that M. catarrhalis causes significant morbidity and is not just a harmless commensal. The universal prevalence of BRO ?-lactamases in this pathogen is a serious concern. In addition, M. catarrhalis may be further propelled into a more prominent position in the hierarchy of respiratory infectious agents due to the phenomenon of ?non-vaccine type replacement? as a result of the wider usage of vaccines against other pathogens in the same ecological niche, such as Haemophilus influenzae and Streptococcus pneumoniae. There is currently no available vaccine against M. catarrhalis. A detailed analysis of the interactions of this bacterium with the human host is necessary to identify ways to interfere with its colonization and infection. To this end, we have focused on the interactions via three outer membrane proteins, namely UspA1 (ubiquitous surface protein A1), UspA2 and MID (Moraxella catarrhalis IgD binding protein). We found that UspA1 and A2 could bind fibronectin and laminin, and characterized these interactions. We also detailed a novel interaction of UspA1 and A2 with the complement protein C3. The UspA1/A2-dependent C3 binding contributes to its serum resistant phenotype and is a way in which M. catarrhalis combat the innate immunity. Furthermore, we showed that this interaction could contribute to the survival of copathogens. An analysis of naturally acquired serological responses to these two proteins and those of MID showed that the functional domains identified here (fibronectin binding region in UspA1299-452 and UspA2165-318, C3 binding region in UspA2) and those identified in other studies (CEACAM binding region of UspA1, the MID764-913 adhesive domain) evoked significant immune responses. The better understanding of the interactions and the identification of important domains in these three proteins represent significant advances in the quest for a suitable vaccine against M. catarrhalis.

AB - Moraxella catarrhalis is an airway pathogen whose role in infection has been increasingly recognized in recent years. Most authorities in this field now agree that M. catarrhalis causes significant morbidity and is not just a harmless commensal. The universal prevalence of BRO ?-lactamases in this pathogen is a serious concern. In addition, M. catarrhalis may be further propelled into a more prominent position in the hierarchy of respiratory infectious agents due to the phenomenon of ?non-vaccine type replacement? as a result of the wider usage of vaccines against other pathogens in the same ecological niche, such as Haemophilus influenzae and Streptococcus pneumoniae. There is currently no available vaccine against M. catarrhalis. A detailed analysis of the interactions of this bacterium with the human host is necessary to identify ways to interfere with its colonization and infection. To this end, we have focused on the interactions via three outer membrane proteins, namely UspA1 (ubiquitous surface protein A1), UspA2 and MID (Moraxella catarrhalis IgD binding protein). We found that UspA1 and A2 could bind fibronectin and laminin, and characterized these interactions. We also detailed a novel interaction of UspA1 and A2 with the complement protein C3. The UspA1/A2-dependent C3 binding contributes to its serum resistant phenotype and is a way in which M. catarrhalis combat the innate immunity. Furthermore, we showed that this interaction could contribute to the survival of copathogens. An analysis of naturally acquired serological responses to these two proteins and those of MID showed that the functional domains identified here (fibronectin binding region in UspA1299-452 and UspA2165-318, C3 binding region in UspA2) and those identified in other studies (CEACAM binding region of UspA1, the MID764-913 adhesive domain) evoked significant immune responses. The better understanding of the interactions and the identification of important domains in these three proteins represent significant advances in the quest for a suitable vaccine against M. catarrhalis.

KW - Mikrobiologi

KW - bakteriologi

KW - virologi

KW - mykologi

KW - virology

KW - mycology

KW - Microbiology

KW - bacteriology

KW - MID

KW - UspA1

KW - UspA2

M3 - Doctoral Thesis (compilation)

SN - 91-85559-77-6

PB - Medical Microbiology, Lund University

ER -

MORAXELLA CATARRHALIS OUTER MEMBRANE PROTEINS AND THEIR INTERACTIONS WITH THE HUMAN HOST

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FN:s Globala mål

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