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Antibody-Mediated Killing of Carbapenem-Resistant ST258 Klebsiella pneumoniae by Human Neutrophils

Carbapenem-resistant Klebsiella pneumoniae is a problem worldwide. A carbapenem-resistant K. pneumoniae lineage classified as multilocus sequence type 258 (ST258) is prominent in the health care setting in many regions of the world, including the United States. ST258 strains can be resistant to virt...

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Autores principales: Kobayashi, Scott D., Porter, Adeline R., Freedman, Brett, Pandey, Ruchi, Chen, Liang, Kreiswirth, Barry N., DeLeo, Frank R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5850326/
https://www.ncbi.nlm.nih.gov/pubmed/29535199
http://dx.doi.org/10.1128/mBio.00297-18
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author Kobayashi, Scott D.
Porter, Adeline R.
Freedman, Brett
Pandey, Ruchi
Chen, Liang
Kreiswirth, Barry N.
DeLeo, Frank R.
author_facet Kobayashi, Scott D.
Porter, Adeline R.
Freedman, Brett
Pandey, Ruchi
Chen, Liang
Kreiswirth, Barry N.
DeLeo, Frank R.
author_sort Kobayashi, Scott D.
collection PubMed
description Carbapenem-resistant Klebsiella pneumoniae is a problem worldwide. A carbapenem-resistant K. pneumoniae lineage classified as multilocus sequence type 258 (ST258) is prominent in the health care setting in many regions of the world, including the United States. ST258 strains can be resistant to virtually all clinically useful antibiotics; treatment of infections caused by these organisms is difficult, and mortality is high. As a step toward promoting development of new therapeutics for ST258 infections, we tested the ability of rabbit antibodies specific for ST258 capsule polysaccharide to enhance human serum bactericidal activity and promote phagocytosis and killing of these bacteria by human neutrophils. We first demonstrated that an isogenic wzy deletion strain is significantly more susceptible to killing by human heparinized blood, serum, and neutrophils than a wild-type ST258 strain. Consistent with the importance of capsule as an immune evasion molecule, rabbit immune serum and purified IgG specific for ST258 capsule polysaccharide type 2 (CPS2) enhanced killing by human blood and serum in vitro. Moreover, antibodies specific for CPS2 promoted phagocytosis and killing of ST258 by human neutrophils. Collectively, our findings suggest that ST258 CPS2 is a viable target for immunoprophylactics and/or therapeutics.
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spelling pubmed-58503262018-03-21 Antibody-Mediated Killing of Carbapenem-Resistant ST258 Klebsiella pneumoniae by Human Neutrophils Kobayashi, Scott D. Porter, Adeline R. Freedman, Brett Pandey, Ruchi Chen, Liang Kreiswirth, Barry N. DeLeo, Frank R. mBio Research Article Carbapenem-resistant Klebsiella pneumoniae is a problem worldwide. A carbapenem-resistant K. pneumoniae lineage classified as multilocus sequence type 258 (ST258) is prominent in the health care setting in many regions of the world, including the United States. ST258 strains can be resistant to virtually all clinically useful antibiotics; treatment of infections caused by these organisms is difficult, and mortality is high. As a step toward promoting development of new therapeutics for ST258 infections, we tested the ability of rabbit antibodies specific for ST258 capsule polysaccharide to enhance human serum bactericidal activity and promote phagocytosis and killing of these bacteria by human neutrophils. We first demonstrated that an isogenic wzy deletion strain is significantly more susceptible to killing by human heparinized blood, serum, and neutrophils than a wild-type ST258 strain. Consistent with the importance of capsule as an immune evasion molecule, rabbit immune serum and purified IgG specific for ST258 capsule polysaccharide type 2 (CPS2) enhanced killing by human blood and serum in vitro. Moreover, antibodies specific for CPS2 promoted phagocytosis and killing of ST258 by human neutrophils. Collectively, our findings suggest that ST258 CPS2 is a viable target for immunoprophylactics and/or therapeutics. American Society for Microbiology 2018-03-13 /pmc/articles/PMC5850326/ /pubmed/29535199 http://dx.doi.org/10.1128/mBio.00297-18 Text en https://www.usa.gov/government-works This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply.
spellingShingle Research Article
Kobayashi, Scott D.
Porter, Adeline R.
Freedman, Brett
Pandey, Ruchi
Chen, Liang
Kreiswirth, Barry N.
DeLeo, Frank R.
Antibody-Mediated Killing of Carbapenem-Resistant ST258 Klebsiella pneumoniae by Human Neutrophils
title Antibody-Mediated Killing of Carbapenem-Resistant ST258 Klebsiella pneumoniae by Human Neutrophils
title_full Antibody-Mediated Killing of Carbapenem-Resistant ST258 Klebsiella pneumoniae by Human Neutrophils
title_fullStr Antibody-Mediated Killing of Carbapenem-Resistant ST258 Klebsiella pneumoniae by Human Neutrophils
title_full_unstemmed Antibody-Mediated Killing of Carbapenem-Resistant ST258 Klebsiella pneumoniae by Human Neutrophils
title_short Antibody-Mediated Killing of Carbapenem-Resistant ST258 Klebsiella pneumoniae by Human Neutrophils
title_sort antibody-mediated killing of carbapenem-resistant st258 klebsiella pneumoniae by human neutrophils
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5850326/
https://www.ncbi.nlm.nih.gov/pubmed/29535199
http://dx.doi.org/10.1128/mBio.00297-18
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