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.
Highlights
The frequency of multidrug (MDR) resistance among pathogenic bacteria, such as New Delhi metallo--lactamase-1 (NDM-1) Klebsiella pneumoniae-induced pneumonia, and the ability of the bacteria to continually evolve in a manner that renders traditional antibiotic treatment ineffective are growing health care concerns around the world
We recently reported that i.n. coadministration of recombinant human cystatins 9 (rCST9)/rCSTC (50 pg of each/mouse) 1 h postinfection (p.i.) followed by a subsequent rCST9/rCSTC dose (500 pg of each/mouse) given intraperitoneally (i.p.) at 3 days p.i. significantly modulated excessive inflammation, decreased apoptosis, preserved the structural integrity of the lung, decreased bacterial load, and significantly increased survival outcomes in our murine model of pneumonia induced by MDR NDM-1 K. pneumoniae [1]
Because high endogenous serum CSTC levels serve as biomarkers that are strongly linked to poor kidney function [9, 10] and cardiovascular damage [11], we sought to evaluate how MDR NDM-1 K. pneumoniae (ATCC BAA 2146)-induced pneumonia and/or rCST treatment affected endogenous CST9 and CSTC serum levels
Summary
The frequency of multidrug (MDR) resistance among pathogenic bacteria, such as New Delhi metallo--lactamase-1 (NDM-1) Klebsiella pneumoniae-induced pneumonia, and the ability of the bacteria to continually evolve in a manner that renders traditional antibiotic treatment ineffective are growing health care concerns around the world. We used the archived serum samples of BALB/c mice (Jackson Laboratories) that were infected and/or treated with rCST9/rCSTC (n ϭ 6 mice/group) from our previously published studies to quantify endogenous serum CST9 and CSTC via enzyme-linked immunosorbent assay (ThermoFisher and Invitrogen, respectively) [1].
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
