Antibody-Mediated Killing of Carbapenem-Resistant ST258 <italic toggle="yes">Klebsiella pneumoniae</italic> by Human Neutrophils

ABSTRACT 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 resistan...

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Autores principales:	Scott D. Kobayashi, Adeline R. Porter, Brett Freedman, Ruchi Pandey, Liang Chen, Barry N. Kreiswirth, Frank R. DeLeo
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	Klebsiella antibiotic resistance antibody carbapenems neutrophils vaccines Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/ede557f692274c47b1d41be9aa0f165f
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spelling	oai:doaj.org-article:ede557f692274c47b1d41be9aa0f165f2021-11-15T15:53:27ZAntibody-Mediated Killing of Carbapenem-Resistant ST258 <italic toggle="yes">Klebsiella pneumoniae</italic> by Human Neutrophils10.1128/mBio.00297-182150-7511https://doaj.org/article/ede557f692274c47b1d41be9aa0f165f2018-05-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00297-18https://doaj.org/toc/2150-7511ABSTRACT 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. IMPORTANCE Infections caused by carbapenem-resistant K. pneumoniae are difficult to treat, and mortality is high. New prophylactic approaches and/or therapeutic measures are needed to prevent or treat infections caused by these multidrug-resistant bacteria. A strain of carbapenem-resistant K. pneumoniae, classified by multilocus sequence typing as ST258, is present in many regions of the world and is the most prominent carbapenem-resistant K. pneumoniae lineage in the United States. Here we show that rabbit antibodies specific for capsule polysaccharide of ST258 significantly enhance human serum bactericidal activity and promote phagocytosis and killing of this pathogen by human neutrophils. These studies have provided strong support for the idea that development of an immunotherapy (vaccine) for carbapenem-resistant K. pneumoniae infections is feasible and has merit.Scott D. KobayashiAdeline R. PorterBrett FreedmanRuchi PandeyLiang ChenBarry N. KreiswirthFrank R. DeLeoAmerican Society for MicrobiologyarticleKlebsiellaantibiotic resistanceantibodycarbapenemsneutrophilsvaccinesMicrobiologyQR1-502ENmBio, Vol 9, Iss 2 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Klebsiella antibiotic resistance antibody carbapenems neutrophils vaccines Microbiology QR1-502
spellingShingle	Klebsiella antibiotic resistance antibody carbapenems neutrophils vaccines Microbiology QR1-502 Scott D. Kobayashi Adeline R. Porter Brett Freedman Ruchi Pandey Liang Chen Barry N. Kreiswirth Frank R. DeLeo Antibody-Mediated Killing of Carbapenem-Resistant ST258 <italic toggle="yes">Klebsiella pneumoniae</italic> by Human Neutrophils
description	ABSTRACT 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. IMPORTANCE Infections caused by carbapenem-resistant K. pneumoniae are difficult to treat, and mortality is high. New prophylactic approaches and/or therapeutic measures are needed to prevent or treat infections caused by these multidrug-resistant bacteria. A strain of carbapenem-resistant K. pneumoniae, classified by multilocus sequence typing as ST258, is present in many regions of the world and is the most prominent carbapenem-resistant K. pneumoniae lineage in the United States. Here we show that rabbit antibodies specific for capsule polysaccharide of ST258 significantly enhance human serum bactericidal activity and promote phagocytosis and killing of this pathogen by human neutrophils. These studies have provided strong support for the idea that development of an immunotherapy (vaccine) for carbapenem-resistant K. pneumoniae infections is feasible and has merit.
format	article
author	Scott D. Kobayashi Adeline R. Porter Brett Freedman Ruchi Pandey Liang Chen Barry N. Kreiswirth Frank R. DeLeo
author_facet	Scott D. Kobayashi Adeline R. Porter Brett Freedman Ruchi Pandey Liang Chen Barry N. Kreiswirth Frank R. DeLeo
author_sort	Scott D. Kobayashi
title	Antibody-Mediated Killing of Carbapenem-Resistant ST258 <italic toggle="yes">Klebsiella pneumoniae</italic> by Human Neutrophils
title_short	Antibody-Mediated Killing of Carbapenem-Resistant ST258 <italic toggle="yes">Klebsiella pneumoniae</italic> by Human Neutrophils
title_full	Antibody-Mediated Killing of Carbapenem-Resistant ST258 <italic toggle="yes">Klebsiella pneumoniae</italic> by Human Neutrophils
title_fullStr	Antibody-Mediated Killing of Carbapenem-Resistant ST258 <italic toggle="yes">Klebsiella pneumoniae</italic> by Human Neutrophils
title_full_unstemmed	Antibody-Mediated Killing of Carbapenem-Resistant ST258 <italic toggle="yes">Klebsiella pneumoniae</italic> by Human Neutrophils
title_sort	antibody-mediated killing of carbapenem-resistant st258 <italic toggle="yes">klebsiella pneumoniae</italic> by human neutrophils
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/ede557f692274c47b1d41be9aa0f165f
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Antibody-Mediated Killing of Carbapenem-Resistant ST258 <italic toggle="yes">Klebsiella pneumoniae</italic> by Human Neutrophils

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