Discovery of monoclonal antibodies cross-reactive to novel subserotypes of K. pneumoniae O3

Abstract Klebsiella pneumoniae is responsible for nosocomial infections causing significant morbidity and mortality. Treatment of newly emerging multi-drug resistant strains is hampered due to severely limited antibiotic choices. Passive immunization targeting LPS O-antigens has been proposed as an...

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Autores principales:	Luis M. Guachalla, Katarina Stojkovic, Katharina Hartl, Marta Kaszowska, Yadhu Kumar, Benjamin Wahl, Tobias Paprotka, Eszter Nagy, Jolanta Lukasiewicz, Gábor Nagy, Valéria Szijártó
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1b7597686aad4c7c8dd38d222080c112
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spelling	oai:doaj.org-article:1b7597686aad4c7c8dd38d222080c1122021-12-02T16:06:33ZDiscovery of monoclonal antibodies cross-reactive to novel subserotypes of K. pneumoniae O310.1038/s41598-017-06682-22045-2322https://doaj.org/article/1b7597686aad4c7c8dd38d222080c1122017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-06682-2https://doaj.org/toc/2045-2322Abstract Klebsiella pneumoniae is responsible for nosocomial infections causing significant morbidity and mortality. Treatment of newly emerging multi-drug resistant strains is hampered due to severely limited antibiotic choices. Passive immunization targeting LPS O-antigens has been proposed as an alternative therapeutic option, given the limited variability of Klebsiella O-antigens. Here we report that the O3 serogroup, previously considered to have uniform O-antigen built of mannan, represents three different subtypes differing in the number of mannose residues within the O-antigen repeating units. Genetic analysis of the genes encoding mannose polymerization revealed differences that underline the observed structural alterations. The O3 variants represent antigenically different types based on the different reactivity pattern of murine monoclonal antibodies raised against a K. pneumoniae O3 strain. Typing of a collection of K. pneumoniae O3 clinical isolates showed that strains expressing the novel O3b antigen, the tri-mannose form, were more prevalent than those having the penta-mannose form, traditionally called O3, while the tetra-mannose variant, termed here O3a, seems to be rare. A monoclonal antibody cross-reacting with all three O3 sub-serogroups was also selected and shown to bind to the surface of various K. pneumoniae strains expressing different O3 subtypes and capsular antigens.Luis M. GuachallaKatarina StojkovicKatharina HartlMarta KaszowskaYadhu KumarBenjamin WahlTobias PaprotkaEszter NagyJolanta LukasiewiczGábor NagyValéria SzijártóNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Luis M. Guachalla Katarina Stojkovic Katharina Hartl Marta Kaszowska Yadhu Kumar Benjamin Wahl Tobias Paprotka Eszter Nagy Jolanta Lukasiewicz Gábor Nagy Valéria Szijártó Discovery of monoclonal antibodies cross-reactive to novel subserotypes of K. pneumoniae O3
description	Abstract Klebsiella pneumoniae is responsible for nosocomial infections causing significant morbidity and mortality. Treatment of newly emerging multi-drug resistant strains is hampered due to severely limited antibiotic choices. Passive immunization targeting LPS O-antigens has been proposed as an alternative therapeutic option, given the limited variability of Klebsiella O-antigens. Here we report that the O3 serogroup, previously considered to have uniform O-antigen built of mannan, represents three different subtypes differing in the number of mannose residues within the O-antigen repeating units. Genetic analysis of the genes encoding mannose polymerization revealed differences that underline the observed structural alterations. The O3 variants represent antigenically different types based on the different reactivity pattern of murine monoclonal antibodies raised against a K. pneumoniae O3 strain. Typing of a collection of K. pneumoniae O3 clinical isolates showed that strains expressing the novel O3b antigen, the tri-mannose form, were more prevalent than those having the penta-mannose form, traditionally called O3, while the tetra-mannose variant, termed here O3a, seems to be rare. A monoclonal antibody cross-reacting with all three O3 sub-serogroups was also selected and shown to bind to the surface of various K. pneumoniae strains expressing different O3 subtypes and capsular antigens.
format	article
author	Luis M. Guachalla Katarina Stojkovic Katharina Hartl Marta Kaszowska Yadhu Kumar Benjamin Wahl Tobias Paprotka Eszter Nagy Jolanta Lukasiewicz Gábor Nagy Valéria Szijártó
author_facet	Luis M. Guachalla Katarina Stojkovic Katharina Hartl Marta Kaszowska Yadhu Kumar Benjamin Wahl Tobias Paprotka Eszter Nagy Jolanta Lukasiewicz Gábor Nagy Valéria Szijártó
author_sort	Luis M. Guachalla
title	Discovery of monoclonal antibodies cross-reactive to novel subserotypes of K. pneumoniae O3
title_short	Discovery of monoclonal antibodies cross-reactive to novel subserotypes of K. pneumoniae O3
title_full	Discovery of monoclonal antibodies cross-reactive to novel subserotypes of K. pneumoniae O3
title_fullStr	Discovery of monoclonal antibodies cross-reactive to novel subserotypes of K. pneumoniae O3
title_full_unstemmed	Discovery of monoclonal antibodies cross-reactive to novel subserotypes of K. pneumoniae O3
title_sort	discovery of monoclonal antibodies cross-reactive to novel subserotypes of k. pneumoniae o3
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/1b7597686aad4c7c8dd38d222080c112
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Discovery of monoclonal antibodies cross-reactive to novel subserotypes of K. pneumoniae O3

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