Combination of Cystatins 9 and C Modulates Serum Biomarkers Associated with Inflammation and Provides Prophylactic as Well as Long-Term Protection against Multidrug-Resistant Klebsiella pneumoniae

Alex J. Holloway, Jieh Juen Yu, Bernard P. Arulanandam, Gregg Milligan, Tonyia Eaves-Pyles

Research output: Contribution to journalArticle

Abstract

We have identified recombinant human cystatins 9 (rCST9) and C (rCSTC) as a combination immunotherapeutic treatment against multidrug-resistant (MDR) New Delhi metallo-lactamase-1 (NDM-1)-producing Klebsiella pneumoniae. We evaluated the lasting protection of rCST9/rCSTC treatment against MDR NDM-1 K. pneumoniae pneumonia. Results showed that rCST9/rCSTC treatment modulated endogenous serum biomarkers, cystatins 9 and C and amyloid A, associated with poor patient outcomes and provided prophylactic and long-term protection in a murine model of pneumonia.

Original languageEnglish (US)
Article numbere02519-18
JournalAntimicrobial Agents and Chemotherapy
Volume63
Issue number5
DOIs
StatePublished - May 1 2019

Fingerprint

Cystatin C
Klebsiella pneumoniae
Cystatins
Biomarkers
Inflammation
Pneumonia
Serum
Amyloid
Therapeutics

Keywords

  • Adoptive B-cell transfer
  • Amyloid A
  • Cystatin 9
  • Cystatin C
  • Immunomodulation
  • Immunotherapy
  • Inflammation
  • Multidrug resistant
  • NDM-1 Klebsiella pneumoniae
  • Pneumonia

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

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title = "Combination of Cystatins 9 and C Modulates Serum Biomarkers Associated with Inflammation and Provides Prophylactic as Well as Long-Term Protection against Multidrug-Resistant Klebsiella pneumoniae",
abstract = "We have identified recombinant human cystatins 9 (rCST9) and C (rCSTC) as a combination immunotherapeutic treatment against multidrug-resistant (MDR) New Delhi metallo-lactamase-1 (NDM-1)-producing Klebsiella pneumoniae. We evaluated the lasting protection of rCST9/rCSTC treatment against MDR NDM-1 K. pneumoniae pneumonia. Results showed that rCST9/rCSTC treatment modulated endogenous serum biomarkers, cystatins 9 and C and amyloid A, associated with poor patient outcomes and provided prophylactic and long-term protection in a murine model of pneumonia.",
keywords = "Adoptive B-cell transfer, Amyloid A, Cystatin 9, Cystatin C, Immunomodulation, Immunotherapy, Inflammation, Multidrug resistant, NDM-1 Klebsiella pneumoniae, Pneumonia",
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publisher = "American Society for Microbiology",
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T1 - Combination of Cystatins 9 and C Modulates Serum Biomarkers Associated with Inflammation and Provides Prophylactic as Well as Long-Term Protection against Multidrug-Resistant Klebsiella pneumoniae

AU - Holloway, Alex J.

AU - Yu, Jieh Juen

AU - Arulanandam, Bernard P.

AU - Milligan, Gregg

AU - Eaves-Pyles, Tonyia

PY - 2019/5/1

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N2 - We have identified recombinant human cystatins 9 (rCST9) and C (rCSTC) as a combination immunotherapeutic treatment against multidrug-resistant (MDR) New Delhi metallo-lactamase-1 (NDM-1)-producing Klebsiella pneumoniae. We evaluated the lasting protection of rCST9/rCSTC treatment against MDR NDM-1 K. pneumoniae pneumonia. Results showed that rCST9/rCSTC treatment modulated endogenous serum biomarkers, cystatins 9 and C and amyloid A, associated with poor patient outcomes and provided prophylactic and long-term protection in a murine model of pneumonia.

AB - We have identified recombinant human cystatins 9 (rCST9) and C (rCSTC) as a combination immunotherapeutic treatment against multidrug-resistant (MDR) New Delhi metallo-lactamase-1 (NDM-1)-producing Klebsiella pneumoniae. We evaluated the lasting protection of rCST9/rCSTC treatment against MDR NDM-1 K. pneumoniae pneumonia. Results showed that rCST9/rCSTC treatment modulated endogenous serum biomarkers, cystatins 9 and C and amyloid A, associated with poor patient outcomes and provided prophylactic and long-term protection in a murine model of pneumonia.

KW - Adoptive B-cell transfer

KW - Amyloid A

KW - Cystatin 9

KW - Cystatin C

KW - Immunomodulation

KW - Immunotherapy

KW - Inflammation

KW - Multidrug resistant

KW - NDM-1 Klebsiella pneumoniae

KW - Pneumonia

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