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

Antimicrob Agents Chemother. 2019 Apr 25;63(5):e02519-18. doi: 10.1128/AAC.02519-18. Print 2019 May.

Abstract

We have identified recombinant human cystatins 9 (rCST9) and C (rCSTC) as a combination immunotherapeutic treatment against multidrug-resistant (MDR) New Delhi metallo-β-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: NDM-1 Klebsiella pneumoniae; adoptive B-cell transfer; amyloid A; cystatin 9; cystatin C; immunomodulation; immunotherapy; inflammation; multidrug resistant; pneumonia.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cystatin C / metabolism
  • Cystatins / blood*
  • Immunomodulation / drug effects
  • Immunotherapy
  • Inflammation / blood*
  • Klebsiella pneumoniae / drug effects
  • Mice
  • Mice, Inbred BALB C
  • Microbial Sensitivity Tests
  • Serum Amyloid A Protein / metabolism

Substances

  • Cystatin C
  • Cystatins
  • Serum Amyloid A Protein