Carbapenem-resistant klebsiella pneumoniae exhibit variability in capsular polysaccharide and capsule associated virulence traits

Elizabeth Diago-Navarro, Liang Chen, Virginie Passet, Seth Burack, Amaia Ulacia-Hernando, Rosy Priya Kodiyanplakkal, Michael H. Levi, Sylvain Brisse, Barry N. Kreiswirth, Bettina C. Fries

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Background. Novel therapies are urgently needed to treat carbapenem-resistant Klebsiella pneumoniae (CRKp)- mediated infection, which constitute a major health threat in the United States. In order to assess if it is feasible to develop anticapsular antibodies as a potential novel therapy, it is crucial to first systematically characterize capsular polysaccharide (CPS) and virulence traits in these strains. Methods. Forty CR-Kp were genotyped by pulsed field gel electrophoresis, multilocus sequence typing (MLST), and molecular capsule typing (C-patterns and wzi sequencing). Their biofilm formation, serum resistance, macrophage- mediated killing, and virulence in Galleria mellonella were compared. MAb (1C9) was generated by coimmunization with 2 CPSs, and cross-reactivity was investigated. Results. MLST assigned 80% of CR-Kp isolates to the ST258-clone. Molecular capsule typing identified new C-patterns, including C200/wzi-154, which was widely represented and associated with blaKPC-3-bearing strains. Heterogeneity was detected in biofilm formation and macrophage-mediated killing. Differences in serum resistance correlated with virulence in G. mellonella. ST258 strains carrying bla<inf>KPC-3</inf> were less virulent than those with bla<inf>KPC-2</inf>. MAb 1C9 cross-reacted with 58% of CR-Kp CPSs. Conclusions. CR-Kp ST258 strains exhibit variability of virulence-associated traits. Differences were associated with the type of KPC gene and CPS. Identification of cross-reacting anti-CPS mAbs encourages their development as adjunctive therapy.

Original languageEnglish (US)
Pages (from-to)803-813
Number of pages11
JournalJournal of Infectious Diseases
Volume210
Issue number5
DOIs
StatePublished - Sep 1 2014

Fingerprint

Carbapenems
Klebsiella pneumoniae
Capsules
Polysaccharides
Virulence
Multilocus Sequence Typing
Molecular Typing
Biofilms
Macrophages
Pulsed Field Gel Electrophoresis
Serum
Therapeutics
Clone Cells
Antibodies
Health
Infection
Genes

Keywords

  • Adjuvant therapy
  • Carbapenem resistance
  • Klebsiella pneumoniae
  • Virulence

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy

Cite this

Diago-Navarro, E., Chen, L., Passet, V., Burack, S., Ulacia-Hernando, A., Kodiyanplakkal, R. P., ... Fries, B. C. (2014). Carbapenem-resistant klebsiella pneumoniae exhibit variability in capsular polysaccharide and capsule associated virulence traits. Journal of Infectious Diseases, 210(5), 803-813. https://doi.org/10.1093/infdis/jiu157

Carbapenem-resistant klebsiella pneumoniae exhibit variability in capsular polysaccharide and capsule associated virulence traits. / Diago-Navarro, Elizabeth; Chen, Liang; Passet, Virginie; Burack, Seth; Ulacia-Hernando, Amaia; Kodiyanplakkal, Rosy Priya; Levi, Michael H.; Brisse, Sylvain; Kreiswirth, Barry N.; Fries, Bettina C.

In: Journal of Infectious Diseases, Vol. 210, No. 5, 01.09.2014, p. 803-813.

Research output: Contribution to journalArticle

Diago-Navarro, E, Chen, L, Passet, V, Burack, S, Ulacia-Hernando, A, Kodiyanplakkal, RP, Levi, MH, Brisse, S, Kreiswirth, BN & Fries, BC 2014, 'Carbapenem-resistant klebsiella pneumoniae exhibit variability in capsular polysaccharide and capsule associated virulence traits', Journal of Infectious Diseases, vol. 210, no. 5, pp. 803-813. https://doi.org/10.1093/infdis/jiu157
Diago-Navarro, Elizabeth ; Chen, Liang ; Passet, Virginie ; Burack, Seth ; Ulacia-Hernando, Amaia ; Kodiyanplakkal, Rosy Priya ; Levi, Michael H. ; Brisse, Sylvain ; Kreiswirth, Barry N. ; Fries, Bettina C. / Carbapenem-resistant klebsiella pneumoniae exhibit variability in capsular polysaccharide and capsule associated virulence traits. In: Journal of Infectious Diseases. 2014 ; Vol. 210, No. 5. pp. 803-813.
@article{7e12e07e82db465e8fd7addfb63365f5,
title = "Carbapenem-resistant klebsiella pneumoniae exhibit variability in capsular polysaccharide and capsule associated virulence traits",
abstract = "Background. Novel therapies are urgently needed to treat carbapenem-resistant Klebsiella pneumoniae (CRKp)- mediated infection, which constitute a major health threat in the United States. In order to assess if it is feasible to develop anticapsular antibodies as a potential novel therapy, it is crucial to first systematically characterize capsular polysaccharide (CPS) and virulence traits in these strains. Methods. Forty CR-Kp were genotyped by pulsed field gel electrophoresis, multilocus sequence typing (MLST), and molecular capsule typing (C-patterns and wzi sequencing). Their biofilm formation, serum resistance, macrophage- mediated killing, and virulence in Galleria mellonella were compared. MAb (1C9) was generated by coimmunization with 2 CPSs, and cross-reactivity was investigated. Results. MLST assigned 80{\%} of CR-Kp isolates to the ST258-clone. Molecular capsule typing identified new C-patterns, including C200/wzi-154, which was widely represented and associated with blaKPC-3-bearing strains. Heterogeneity was detected in biofilm formation and macrophage-mediated killing. Differences in serum resistance correlated with virulence in G. mellonella. ST258 strains carrying blaKPC-3 were less virulent than those with blaKPC-2. MAb 1C9 cross-reacted with 58{\%} of CR-Kp CPSs. Conclusions. CR-Kp ST258 strains exhibit variability of virulence-associated traits. Differences were associated with the type of KPC gene and CPS. Identification of cross-reacting anti-CPS mAbs encourages their development as adjunctive therapy.",
keywords = "Adjuvant therapy, Carbapenem resistance, Klebsiella pneumoniae, Virulence",
author = "Elizabeth Diago-Navarro and Liang Chen and Virginie Passet and Seth Burack and Amaia Ulacia-Hernando and Kodiyanplakkal, {Rosy Priya} and Levi, {Michael H.} and Sylvain Brisse and Kreiswirth, {Barry N.} and Fries, {Bettina C.}",
year = "2014",
month = "9",
day = "1",
doi = "10.1093/infdis/jiu157",
language = "English (US)",
volume = "210",
pages = "803--813",
journal = "Journal of Infectious Diseases",
issn = "0022-1899",
publisher = "Oxford University Press",
number = "5",

}

TY - JOUR

T1 - Carbapenem-resistant klebsiella pneumoniae exhibit variability in capsular polysaccharide and capsule associated virulence traits

AU - Diago-Navarro, Elizabeth

AU - Chen, Liang

AU - Passet, Virginie

AU - Burack, Seth

AU - Ulacia-Hernando, Amaia

AU - Kodiyanplakkal, Rosy Priya

AU - Levi, Michael H.

AU - Brisse, Sylvain

AU - Kreiswirth, Barry N.

AU - Fries, Bettina C.

PY - 2014/9/1

Y1 - 2014/9/1

N2 - Background. Novel therapies are urgently needed to treat carbapenem-resistant Klebsiella pneumoniae (CRKp)- mediated infection, which constitute a major health threat in the United States. In order to assess if it is feasible to develop anticapsular antibodies as a potential novel therapy, it is crucial to first systematically characterize capsular polysaccharide (CPS) and virulence traits in these strains. Methods. Forty CR-Kp were genotyped by pulsed field gel electrophoresis, multilocus sequence typing (MLST), and molecular capsule typing (C-patterns and wzi sequencing). Their biofilm formation, serum resistance, macrophage- mediated killing, and virulence in Galleria mellonella were compared. MAb (1C9) was generated by coimmunization with 2 CPSs, and cross-reactivity was investigated. Results. MLST assigned 80% of CR-Kp isolates to the ST258-clone. Molecular capsule typing identified new C-patterns, including C200/wzi-154, which was widely represented and associated with blaKPC-3-bearing strains. Heterogeneity was detected in biofilm formation and macrophage-mediated killing. Differences in serum resistance correlated with virulence in G. mellonella. ST258 strains carrying blaKPC-3 were less virulent than those with blaKPC-2. MAb 1C9 cross-reacted with 58% of CR-Kp CPSs. Conclusions. CR-Kp ST258 strains exhibit variability of virulence-associated traits. Differences were associated with the type of KPC gene and CPS. Identification of cross-reacting anti-CPS mAbs encourages their development as adjunctive therapy.

AB - Background. Novel therapies are urgently needed to treat carbapenem-resistant Klebsiella pneumoniae (CRKp)- mediated infection, which constitute a major health threat in the United States. In order to assess if it is feasible to develop anticapsular antibodies as a potential novel therapy, it is crucial to first systematically characterize capsular polysaccharide (CPS) and virulence traits in these strains. Methods. Forty CR-Kp were genotyped by pulsed field gel electrophoresis, multilocus sequence typing (MLST), and molecular capsule typing (C-patterns and wzi sequencing). Their biofilm formation, serum resistance, macrophage- mediated killing, and virulence in Galleria mellonella were compared. MAb (1C9) was generated by coimmunization with 2 CPSs, and cross-reactivity was investigated. Results. MLST assigned 80% of CR-Kp isolates to the ST258-clone. Molecular capsule typing identified new C-patterns, including C200/wzi-154, which was widely represented and associated with blaKPC-3-bearing strains. Heterogeneity was detected in biofilm formation and macrophage-mediated killing. Differences in serum resistance correlated with virulence in G. mellonella. ST258 strains carrying blaKPC-3 were less virulent than those with blaKPC-2. MAb 1C9 cross-reacted with 58% of CR-Kp CPSs. Conclusions. CR-Kp ST258 strains exhibit variability of virulence-associated traits. Differences were associated with the type of KPC gene and CPS. Identification of cross-reacting anti-CPS mAbs encourages their development as adjunctive therapy.

KW - Adjuvant therapy

KW - Carbapenem resistance

KW - Klebsiella pneumoniae

KW - Virulence

UR - http://www.scopus.com/inward/record.url?scp=84901282068&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84901282068&partnerID=8YFLogxK

U2 - 10.1093/infdis/jiu157

DO - 10.1093/infdis/jiu157

M3 - Article

VL - 210

SP - 803

EP - 813

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

SN - 0022-1899

IS - 5

ER -