Degradation of host defence molecules by CF-related pathogens grown as biofilms

G. G. Einarsson, S. L. Martin, B. Walker, J. S Elborn, A. McDowell

    Research output: Chapter in Book/Report/Conference proceedingConference contribution

    Abstract

    We investigated the ability of secreted bacterial proteinases from three pathogens [Burkholderia multivorans (Bm), Burkholderia cenocepacia (Bc), and Pseudomonas aeruginosa (Pa)] involved in chronic bacterial infections in cystic fibrosis to degrade various host defence-related molecules. These included two endogenous proteinase inhibitors, secretory leukocyte proteinase inhibitor (rhSLPI) and alpha-1 antitrypsin (AAT); two relevant immunoglobulins, secretory IgA (sIgA) and IgG, and two proteins important in innate immunity, lactoferrin and lysozyme. Host defence-related molecules were co-incubated with cell-free supernatants from 48 hour biofilm cultures, grown on mucin-coated microplates, from all three pathogens under investigation (six isolates from each species). No degradation of AAT, sIgA, IgG, and lactoferrin was observed for any of the organisms. Of the 18 isolates tested, only one demonstrated the ability to degrade lysozyme. This was an environmental isolate of Pa which was included as a comparison for the predominantly clinically relevant isolates used in the study. In contrast, all isolates of Bm (n = 4) and Pa (n = 4) were able to degrade rhSLPI however, out of five bacterial isolates tested for Bc only two demonstrated a limited ability to degrade the molecule with >95% of the protein band still remaining intact at the end of the experiment. This study demonstrates that the majority of the host defence molecules investigated are resistant to degradation by bacterial proteinases from Bm, Bc and Pa when grown as a biofilm. However, rhSLPI was vulnerable to significant degradation which could result in aberrant serine proteolysis in regions of the lungs containing biofilm growth.
    LanguageEnglish
    Title of host publicationUnknown Host Publication
    PagesS43-S43
    Number of pages1
    Publication statusPublished - 2008
    Event31st European Cystic Fibrosis Conference - Prague, Czech Republic
    Duration: 1 Jan 2008 → …

    Conference

    Conference31st European Cystic Fibrosis Conference
    Period1/01/08 → …

    Fingerprint

    Burkholderia cenocepacia
    Biofilms
    Burkholderia
    Pseudomonas aeruginosa
    Peptide Hydrolases
    Secretory Immunoglobulin A
    alpha 1-Antitrypsin
    Lactoferrin
    Muramidase
    Immunoglobulin G
    Mucins
    Bacterial Infections
    Innate Immunity
    Cystic Fibrosis
    Serine
    Proteolysis
    Immunoglobulins
    Proteins
    Leukocytes
    Lung

    Cite this

    Einarsson, G. G., Martin, S. L., Walker, B., Elborn, J. S., & McDowell, A. (2008). Degradation of host defence molecules by CF-related pathogens grown as biofilms. In Unknown Host Publication (pp. S43-S43)
    Einarsson, G. G. ; Martin, S. L. ; Walker, B. ; Elborn, J. S ; McDowell, A. / Degradation of host defence molecules by CF-related pathogens grown as biofilms. Unknown Host Publication. 2008. pp. S43-S43
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    abstract = "We investigated the ability of secreted bacterial proteinases from three pathogens [Burkholderia multivorans (Bm), Burkholderia cenocepacia (Bc), and Pseudomonas aeruginosa (Pa)] involved in chronic bacterial infections in cystic fibrosis to degrade various host defence-related molecules. These included two endogenous proteinase inhibitors, secretory leukocyte proteinase inhibitor (rhSLPI) and alpha-1 antitrypsin (AAT); two relevant immunoglobulins, secretory IgA (sIgA) and IgG, and two proteins important in innate immunity, lactoferrin and lysozyme. Host defence-related molecules were co-incubated with cell-free supernatants from 48 hour biofilm cultures, grown on mucin-coated microplates, from all three pathogens under investigation (six isolates from each species). No degradation of AAT, sIgA, IgG, and lactoferrin was observed for any of the organisms. Of the 18 isolates tested, only one demonstrated the ability to degrade lysozyme. This was an environmental isolate of Pa which was included as a comparison for the predominantly clinically relevant isolates used in the study. In contrast, all isolates of Bm (n = 4) and Pa (n = 4) were able to degrade rhSLPI however, out of five bacterial isolates tested for Bc only two demonstrated a limited ability to degrade the molecule with >95{\%} of the protein band still remaining intact at the end of the experiment. This study demonstrates that the majority of the host defence molecules investigated are resistant to degradation by bacterial proteinases from Bm, Bc and Pa when grown as a biofilm. However, rhSLPI was vulnerable to significant degradation which could result in aberrant serine proteolysis in regions of the lungs containing biofilm growth.",
    author = "Einarsson, {G. G.} and Martin, {S. L.} and B. Walker and Elborn, {J. S} and A. McDowell",
    year = "2008",
    language = "English",
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    Einarsson, GG, Martin, SL, Walker, B, Elborn, JS & McDowell, A 2008, Degradation of host defence molecules by CF-related pathogens grown as biofilms. in Unknown Host Publication. pp. S43-S43, 31st European Cystic Fibrosis Conference, 1/01/08.

    Degradation of host defence molecules by CF-related pathogens grown as biofilms. / Einarsson, G. G.; Martin, S. L.; Walker, B.; Elborn, J. S; McDowell, A.

    Unknown Host Publication. 2008. p. S43-S43.

    Research output: Chapter in Book/Report/Conference proceedingConference contribution

    TY - GEN

    T1 - Degradation of host defence molecules by CF-related pathogens grown as biofilms

    AU - Einarsson, G. G.

    AU - Martin, S. L.

    AU - Walker, B.

    AU - Elborn, J. S

    AU - McDowell, A.

    PY - 2008

    Y1 - 2008

    N2 - We investigated the ability of secreted bacterial proteinases from three pathogens [Burkholderia multivorans (Bm), Burkholderia cenocepacia (Bc), and Pseudomonas aeruginosa (Pa)] involved in chronic bacterial infections in cystic fibrosis to degrade various host defence-related molecules. These included two endogenous proteinase inhibitors, secretory leukocyte proteinase inhibitor (rhSLPI) and alpha-1 antitrypsin (AAT); two relevant immunoglobulins, secretory IgA (sIgA) and IgG, and two proteins important in innate immunity, lactoferrin and lysozyme. Host defence-related molecules were co-incubated with cell-free supernatants from 48 hour biofilm cultures, grown on mucin-coated microplates, from all three pathogens under investigation (six isolates from each species). No degradation of AAT, sIgA, IgG, and lactoferrin was observed for any of the organisms. Of the 18 isolates tested, only one demonstrated the ability to degrade lysozyme. This was an environmental isolate of Pa which was included as a comparison for the predominantly clinically relevant isolates used in the study. In contrast, all isolates of Bm (n = 4) and Pa (n = 4) were able to degrade rhSLPI however, out of five bacterial isolates tested for Bc only two demonstrated a limited ability to degrade the molecule with >95% of the protein band still remaining intact at the end of the experiment. This study demonstrates that the majority of the host defence molecules investigated are resistant to degradation by bacterial proteinases from Bm, Bc and Pa when grown as a biofilm. However, rhSLPI was vulnerable to significant degradation which could result in aberrant serine proteolysis in regions of the lungs containing biofilm growth.

    AB - We investigated the ability of secreted bacterial proteinases from three pathogens [Burkholderia multivorans (Bm), Burkholderia cenocepacia (Bc), and Pseudomonas aeruginosa (Pa)] involved in chronic bacterial infections in cystic fibrosis to degrade various host defence-related molecules. These included two endogenous proteinase inhibitors, secretory leukocyte proteinase inhibitor (rhSLPI) and alpha-1 antitrypsin (AAT); two relevant immunoglobulins, secretory IgA (sIgA) and IgG, and two proteins important in innate immunity, lactoferrin and lysozyme. Host defence-related molecules were co-incubated with cell-free supernatants from 48 hour biofilm cultures, grown on mucin-coated microplates, from all three pathogens under investigation (six isolates from each species). No degradation of AAT, sIgA, IgG, and lactoferrin was observed for any of the organisms. Of the 18 isolates tested, only one demonstrated the ability to degrade lysozyme. This was an environmental isolate of Pa which was included as a comparison for the predominantly clinically relevant isolates used in the study. In contrast, all isolates of Bm (n = 4) and Pa (n = 4) were able to degrade rhSLPI however, out of five bacterial isolates tested for Bc only two demonstrated a limited ability to degrade the molecule with >95% of the protein band still remaining intact at the end of the experiment. This study demonstrates that the majority of the host defence molecules investigated are resistant to degradation by bacterial proteinases from Bm, Bc and Pa when grown as a biofilm. However, rhSLPI was vulnerable to significant degradation which could result in aberrant serine proteolysis in regions of the lungs containing biofilm growth.

    M3 - Conference contribution

    SP - S43-S43

    BT - Unknown Host Publication

    ER -

    Einarsson GG, Martin SL, Walker B, Elborn JS, McDowell A. Degradation of host defence molecules by CF-related pathogens grown as biofilms. In Unknown Host Publication. 2008. p. S43-S43