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 N. Milligan; Tonyia D. Eaves-Pyles

doi:10.1128/AAC.02519-18

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 N. Milligan, Tonyia D. Eaves-Pyles

Pediatrics

Research output: Contribution to journal › Article › peer-review

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 language	English (US)
Article number	e02519-18
Journal	Antimicrobial agents and chemotherapy
Volume	63
Issue number	5
DOIs	https://doi.org/10.1128/AAC.02519-18
State	Published - May 2019

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

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10.1128/AAC.02519-18

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Holloway, A. J., Yu, J. J., Arulanandam, B. P., Milligan, G. N., & Eaves-Pyles, T. D. (2019). 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. Antimicrobial agents and chemotherapy, 63(5), Article e02519-18. https://doi.org/10.1128/AAC.02519-18

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. / Holloway, Alex J.; Yu, Jieh Juen; Arulanandam, Bernard P. et al.
In: Antimicrobial agents and chemotherapy, Vol. 63, No. 5, e02519-18, 05.2019.

Research output: Contribution to journal › Article › peer-review

Holloway, AJ, Yu, JJ, Arulanandam, BP, Milligan, GN & Eaves-Pyles, TD 2019, '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', Antimicrobial agents and chemotherapy, vol. 63, no. 5, e02519-18. https://doi.org/10.1128/AAC.02519-18

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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",

author = "Holloway, {Alex J.} and Yu, {Jieh Juen} and Arulanandam, {Bernard P.} and Milligan, {Gregg N.} and Eaves-Pyles, {Tonyia D.}",

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AU - Milligan, Gregg N.

AU - Eaves-Pyles, Tonyia D.

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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.

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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

Keywords

ASJC Scopus subject areas

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