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The Capsule Regulatory Network of Klebsiella pneumoniae Defined by density-TraDISort

Klebsiella pneumoniae infections affect infants and the immunocompromised, and the recent emergence of hypervirulent and multidrug-resistant K. pneumoniae lineages is a critical health care concern. Hypervirulence in K. pneumoniae is mediated by several factors, including the overproduction of extra...

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Autores principales: Dorman, Matthew J., Feltwell, Theresa, Goulding, David A., Parkhill, Julian, Short, Francesca L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6247091/
https://www.ncbi.nlm.nih.gov/pubmed/30459193
http://dx.doi.org/10.1128/mBio.01863-18
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author Dorman, Matthew J.
Feltwell, Theresa
Goulding, David A.
Parkhill, Julian
Short, Francesca L.
author_facet Dorman, Matthew J.
Feltwell, Theresa
Goulding, David A.
Parkhill, Julian
Short, Francesca L.
author_sort Dorman, Matthew J.
collection PubMed
description Klebsiella pneumoniae infections affect infants and the immunocompromised, and the recent emergence of hypervirulent and multidrug-resistant K. pneumoniae lineages is a critical health care concern. Hypervirulence in K. pneumoniae is mediated by several factors, including the overproduction of extracellular capsule. However, the full details of how K. pneumoniae capsule biosynthesis is achieved or regulated are not known. We have developed a robust and sensitive procedure to identify genes influencing capsule production, density-TraDISort, which combines density gradient centrifugation with transposon insertion sequencing. We have used this method to explore capsule regulation in two clinically relevant Klebsiella strains, K. pneumoniae NTUH-K2044 (capsule type K1) and K. pneumoniae ATCC 43816 (capsule type K2). We identified multiple genes required for full capsule production in K. pneumoniae, as well as putative suppressors of capsule in NTUH-K2044, and have validated the results of our screen with targeted knockout mutants. Further investigation of several of the K. pneumoniae capsule regulators identified—ArgR, MprA/KvrB, SlyA/KvrA, and the Sap ABC transporter—revealed effects on capsule amount and architecture, serum resistance, and virulence. We show that capsule production in K. pneumoniae is at the center of a complex regulatory network involving multiple global regulators and environmental cues and that the majority of capsule regulatory genes are located in the core genome. Overall, our findings expand our understanding of how capsule is regulated in this medically important pathogen and provide a technology that can be easily implemented to study capsule regulation in other bacterial species.
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spelling pubmed-62470912018-11-30 The Capsule Regulatory Network of Klebsiella pneumoniae Defined by density-TraDISort Dorman, Matthew J. Feltwell, Theresa Goulding, David A. Parkhill, Julian Short, Francesca L. mBio Research Article Klebsiella pneumoniae infections affect infants and the immunocompromised, and the recent emergence of hypervirulent and multidrug-resistant K. pneumoniae lineages is a critical health care concern. Hypervirulence in K. pneumoniae is mediated by several factors, including the overproduction of extracellular capsule. However, the full details of how K. pneumoniae capsule biosynthesis is achieved or regulated are not known. We have developed a robust and sensitive procedure to identify genes influencing capsule production, density-TraDISort, which combines density gradient centrifugation with transposon insertion sequencing. We have used this method to explore capsule regulation in two clinically relevant Klebsiella strains, K. pneumoniae NTUH-K2044 (capsule type K1) and K. pneumoniae ATCC 43816 (capsule type K2). We identified multiple genes required for full capsule production in K. pneumoniae, as well as putative suppressors of capsule in NTUH-K2044, and have validated the results of our screen with targeted knockout mutants. Further investigation of several of the K. pneumoniae capsule regulators identified—ArgR, MprA/KvrB, SlyA/KvrA, and the Sap ABC transporter—revealed effects on capsule amount and architecture, serum resistance, and virulence. We show that capsule production in K. pneumoniae is at the center of a complex regulatory network involving multiple global regulators and environmental cues and that the majority of capsule regulatory genes are located in the core genome. Overall, our findings expand our understanding of how capsule is regulated in this medically important pathogen and provide a technology that can be easily implemented to study capsule regulation in other bacterial species. American Society for Microbiology 2018-11-20 /pmc/articles/PMC6247091/ /pubmed/30459193 http://dx.doi.org/10.1128/mBio.01863-18 Text en Copyright © 2018 Dorman et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Research Article
Dorman, Matthew J.
Feltwell, Theresa
Goulding, David A.
Parkhill, Julian
Short, Francesca L.
The Capsule Regulatory Network of Klebsiella pneumoniae Defined by density-TraDISort
title The Capsule Regulatory Network of Klebsiella pneumoniae Defined by density-TraDISort
title_full The Capsule Regulatory Network of Klebsiella pneumoniae Defined by density-TraDISort
title_fullStr The Capsule Regulatory Network of Klebsiella pneumoniae Defined by density-TraDISort
title_full_unstemmed The Capsule Regulatory Network of Klebsiella pneumoniae Defined by density-TraDISort
title_short The Capsule Regulatory Network of Klebsiella pneumoniae Defined by density-TraDISort
title_sort capsule regulatory network of klebsiella pneumoniae defined by density-tradisort
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6247091/
https://www.ncbi.nlm.nih.gov/pubmed/30459193
http://dx.doi.org/10.1128/mBio.01863-18
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