The Mutation in wbaP cps Gene Cluster Selected by Phage-Borne Depolymerase Abolishes Capsule Production and Diminishes the Virulence of Klebsiella pneumoniae

Klebsiella pneumoniae is considered one of the most critical multidrug-resistant pathogens and urgently requires new therapeutic strategies. Capsular polysaccharides (CPS), lipopolysaccharides (LPS), and exopolysaccharides (EPS) are the major virulence factors protecting ...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Marta Kaszowska, Grazyna Majkowska-Skrobek, Pawel Markwitz, Cédric Lood, Wojciech Jachymek, Anna Maciejewska, Jolanta Lukasiewicz, Zuzanna Drulis-Kawa
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	<i>Klebsiella</i> phage capsule degrading depolymerase phage resistant mutant capsular polysaccharide Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/e4b8bc86bdb742698ded9020d437732a
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:e4b8bc86bdb742698ded9020d437732a
record_format	dspace
spelling	oai:doaj.org-article:e4b8bc86bdb742698ded9020d437732a2021-11-11T17:02:41ZThe Mutation in <i>wbaP cps</i> Gene Cluster Selected by Phage-Borne Depolymerase Abolishes Capsule Production and Diminishes the Virulence of <i>Klebsiella pneumoniae</i>10.3390/ijms2221115621422-00671661-6596https://doaj.org/article/e4b8bc86bdb742698ded9020d437732a2021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11562https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067<i>Klebsiella pneumoniae</i> is considered one of the most critical multidrug-resistant pathogens and urgently requires new therapeutic strategies. Capsular polysaccharides (CPS), lipopolysaccharides (LPS), and exopolysaccharides (EPS) are the major virulence factors protecting <i>K. pneumoniae</i> against the immune response and thus may be targeted by phage-based therapeutics such as polysaccharides-degrading enzymes. Since the emergence of resistance to antibacterials is generally considered undesirable, in this study, the genetic and phenotypic characteristics of resistance to the phage-borne CPS-degrading depolymerase and its effect on <i>K. pneumoniae</i> virulence were investigated. The K63 serotype targeting depolymerase (KP36gp50) derived from <i>Klebsiella</i> siphovirus KP36 was used as the selective agent during the treatment of <i>K. pneumoniae</i> 486 biofilm. Genome-driven examination combined with the surface polysaccharide structural analysis of resistant mutant showed the point mutation and frameshift in the <i>wbaP</i> gene located within the <i>cps</i> gene cluster, resulting in the loss of the capsule. The sharp decline in the yield of CPS was accompanied by the production of a larger amount of smooth LPS. The modification of the surface polysaccharide layers did not affect bacterial fitness nor the insensitivity to serum complement; however, it made bacteria more prone to phagocytosis combined with the higher adherence and internalization to human lung epithelial cells. In that context, it was showed that the emerging resistance to the antivirulence agent (phage-borne capsule depolymerase) results in beneficial consequences, i.e., the sensitization to the innate immune response.Marta KaszowskaGrazyna Majkowska-SkrobekPawel MarkwitzCédric LoodWojciech JachymekAnna MaciejewskaJolanta LukasiewiczZuzanna Drulis-KawaMDPI AGarticle<i>Klebsiella</i> phagecapsule degrading depolymerasephage resistant mutantcapsular polysaccharideBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11562, p 11562 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	<i>Klebsiella</i> phage capsule degrading depolymerase phage resistant mutant capsular polysaccharide Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	<i>Klebsiella</i> phage capsule degrading depolymerase phage resistant mutant capsular polysaccharide Biology (General) QH301-705.5 Chemistry QD1-999 Marta Kaszowska Grazyna Majkowska-Skrobek Pawel Markwitz Cédric Lood Wojciech Jachymek Anna Maciejewska Jolanta Lukasiewicz Zuzanna Drulis-Kawa The Mutation in <i>wbaP cps</i> Gene Cluster Selected by Phage-Borne Depolymerase Abolishes Capsule Production and Diminishes the Virulence of <i>Klebsiella pneumoniae</i>
description	<i>Klebsiella pneumoniae</i> is considered one of the most critical multidrug-resistant pathogens and urgently requires new therapeutic strategies. Capsular polysaccharides (CPS), lipopolysaccharides (LPS), and exopolysaccharides (EPS) are the major virulence factors protecting <i>K. pneumoniae</i> against the immune response and thus may be targeted by phage-based therapeutics such as polysaccharides-degrading enzymes. Since the emergence of resistance to antibacterials is generally considered undesirable, in this study, the genetic and phenotypic characteristics of resistance to the phage-borne CPS-degrading depolymerase and its effect on <i>K. pneumoniae</i> virulence were investigated. The K63 serotype targeting depolymerase (KP36gp50) derived from <i>Klebsiella</i> siphovirus KP36 was used as the selective agent during the treatment of <i>K. pneumoniae</i> 486 biofilm. Genome-driven examination combined with the surface polysaccharide structural analysis of resistant mutant showed the point mutation and frameshift in the <i>wbaP</i> gene located within the <i>cps</i> gene cluster, resulting in the loss of the capsule. The sharp decline in the yield of CPS was accompanied by the production of a larger amount of smooth LPS. The modification of the surface polysaccharide layers did not affect bacterial fitness nor the insensitivity to serum complement; however, it made bacteria more prone to phagocytosis combined with the higher adherence and internalization to human lung epithelial cells. In that context, it was showed that the emerging resistance to the antivirulence agent (phage-borne capsule depolymerase) results in beneficial consequences, i.e., the sensitization to the innate immune response.
format	article
author	Marta Kaszowska Grazyna Majkowska-Skrobek Pawel Markwitz Cédric Lood Wojciech Jachymek Anna Maciejewska Jolanta Lukasiewicz Zuzanna Drulis-Kawa
author_facet	Marta Kaszowska Grazyna Majkowska-Skrobek Pawel Markwitz Cédric Lood Wojciech Jachymek Anna Maciejewska Jolanta Lukasiewicz Zuzanna Drulis-Kawa
author_sort	Marta Kaszowska
title	The Mutation in <i>wbaP cps</i> Gene Cluster Selected by Phage-Borne Depolymerase Abolishes Capsule Production and Diminishes the Virulence of <i>Klebsiella pneumoniae</i>
title_short	The Mutation in <i>wbaP cps</i> Gene Cluster Selected by Phage-Borne Depolymerase Abolishes Capsule Production and Diminishes the Virulence of <i>Klebsiella pneumoniae</i>
title_full	The Mutation in <i>wbaP cps</i> Gene Cluster Selected by Phage-Borne Depolymerase Abolishes Capsule Production and Diminishes the Virulence of <i>Klebsiella pneumoniae</i>
title_fullStr	The Mutation in <i>wbaP cps</i> Gene Cluster Selected by Phage-Borne Depolymerase Abolishes Capsule Production and Diminishes the Virulence of <i>Klebsiella pneumoniae</i>
title_full_unstemmed	The Mutation in <i>wbaP cps</i> Gene Cluster Selected by Phage-Borne Depolymerase Abolishes Capsule Production and Diminishes the Virulence of <i>Klebsiella pneumoniae</i>
title_sort	mutation in <i>wbap cps</i> gene cluster selected by phage-borne depolymerase abolishes capsule production and diminishes the virulence of <i>klebsiella pneumoniae</i>
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/e4b8bc86bdb742698ded9020d437732a
work_keys_str_mv	AT martakaszowska themutationiniwbapcpsigeneclusterselectedbyphagebornedepolymeraseabolishescapsuleproductionanddiminishesthevirulenceofiklebsiellapneumoniaei AT grazynamajkowskaskrobek themutationiniwbapcpsigeneclusterselectedbyphagebornedepolymeraseabolishescapsuleproductionanddiminishesthevirulenceofiklebsiellapneumoniaei AT pawelmarkwitz themutationiniwbapcpsigeneclusterselectedbyphagebornedepolymeraseabolishescapsuleproductionanddiminishesthevirulenceofiklebsiellapneumoniaei AT cedriclood themutationiniwbapcpsigeneclusterselectedbyphagebornedepolymeraseabolishescapsuleproductionanddiminishesthevirulenceofiklebsiellapneumoniaei AT wojciechjachymek themutationiniwbapcpsigeneclusterselectedbyphagebornedepolymeraseabolishescapsuleproductionanddiminishesthevirulenceofiklebsiellapneumoniaei AT annamaciejewska themutationiniwbapcpsigeneclusterselectedbyphagebornedepolymeraseabolishescapsuleproductionanddiminishesthevirulenceofiklebsiellapneumoniaei AT jolantalukasiewicz themutationiniwbapcpsigeneclusterselectedbyphagebornedepolymeraseabolishescapsuleproductionanddiminishesthevirulenceofiklebsiellapneumoniaei AT zuzannadruliskawa themutationiniwbapcpsigeneclusterselectedbyphagebornedepolymeraseabolishescapsuleproductionanddiminishesthevirulenceofiklebsiellapneumoniaei AT martakaszowska mutationiniwbapcpsigeneclusterselectedbyphagebornedepolymeraseabolishescapsuleproductionanddiminishesthevirulenceofiklebsiellapneumoniaei AT grazynamajkowskaskrobek mutationiniwbapcpsigeneclusterselectedbyphagebornedepolymeraseabolishescapsuleproductionanddiminishesthevirulenceofiklebsiellapneumoniaei AT pawelmarkwitz mutationiniwbapcpsigeneclusterselectedbyphagebornedepolymeraseabolishescapsuleproductionanddiminishesthevirulenceofiklebsiellapneumoniaei AT cedriclood mutationiniwbapcpsigeneclusterselectedbyphagebornedepolymeraseabolishescapsuleproductionanddiminishesthevirulenceofiklebsiellapneumoniaei AT wojciechjachymek mutationiniwbapcpsigeneclusterselectedbyphagebornedepolymeraseabolishescapsuleproductionanddiminishesthevirulenceofiklebsiellapneumoniaei AT annamaciejewska mutationiniwbapcpsigeneclusterselectedbyphagebornedepolymeraseabolishescapsuleproductionanddiminishesthevirulenceofiklebsiellapneumoniaei AT jolantalukasiewicz mutationiniwbapcpsigeneclusterselectedbyphagebornedepolymeraseabolishescapsuleproductionanddiminishesthevirulenceofiklebsiellapneumoniaei AT zuzannadruliskawa mutationiniwbapcpsigeneclusterselectedbyphagebornedepolymeraseabolishescapsuleproductionanddiminishesthevirulenceofiklebsiellapneumoniaei
_version_	1718432208905043968

The Mutation in <i>wbaP cps</i> Gene Cluster Selected by Phage-Borne Depolymerase Abolishes Capsule Production and Diminishes the Virulence of <i>Klebsiella pneumoniae</i>

Ejemplares similares