Please use this identifier to cite or link to this item: http://lib.jncasr.ac.in:8080/jspui/handle/10572/2013
Title: Membrane-Active Macromolecules Resensitize NDM-1 Gram-Negative Clinical Isolates to Tetracycline Antibiotics
Authors: Uppu, Divakara S. S. M.
Manjunath, Goutham B.
Yarlagadda, Venkateswarlu
Kaviyil, Jyothi E.
Ravikumar, Raju
Paramanandham, Krishnamoorthy
Shome, Bibek R.
Haldar, Jayanta
Keywords: Multidisciplinary Sciences
Escherichia-Coli
Acinetobacter-Baumannii
Klebsiella-Pneumoniae
Resistance
Bacteria
Polymers
Mechanisms
Design
Agents
Issue Date: 2015
Publisher: Public Library Science
Citation: PLoS One
10
3
Uppu, D.; Manjunath, G. B.; Yarlagadda, V.; Kaviyil, J. E.; Ravikumar, R.; Paramanandham, K.; Shome, B. R.; Haldar, J., Membrane-Active Macromolecules Resensitize NDM-1 Gram-Negative Clinical Isolates to Tetracycline Antibiotics. PLoS One 2015, 10 (3), 16.
Abstract: Gram-negative 'superbugs' such as New Delhi metallo-beta-lactamase-1 (bla(NDM-1)) producing pathogens have become world's major public health threats. Development of molecular strategies that can rehabilitate the 'old antibiotics' and halt the antibiotic resistance is a promising approach to target them. We report membrane-active macromolecules (MAMs) that restore the antibacterial efficacy (enhancement by >80-1250 fold) of tetracycline antibiotics towards blaNDM-1 Klebsiella pneumonia and blaNDM-1 Escherichia coli clinical isolates. Organismic studies showed that bacteria had an increased and faster uptake of tetracycline in the presence of MAMs which is attributed to the mechanism of re-sensitization. Moreover, bacteria did not develop resistance to MAMs and MAMs stalled the development of bacterial resistance to tetracycline. MAMs displayed membrane-active properties such as dissipation of membrane potential and membrane-permeabilization that enabled higher uptake of tetracycline in bacteria. In-vivo toxicity studies displayed good safety profiles and preliminary in-vivo antibacterial efficacy studies showed that mice treated with MAMs in combination with antibiotics had significantly decreased bacterial burden compared to the untreated mice. This report of re-instating the efficacy of the antibiotics towards blaNDM-1 pathogens using membrane-active molecules advocates their potential for synergistic co-delivery of antibiotics to combat Gram-negative superbugs.
Description: Restricted access
URI: http://hdl.handle.net/10572/2013
ISSN: 1932-6203
Appears in Collections:Research Papers (Jayanta Haldar)

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