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Membrane-Active Macromolecules Resensitize NDM-1 Gram-Negative Clinical Isolates to Tetracycline Antibiotics

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dc.contributor.author Uppu, Divakara S. S. M.
dc.contributor.author Manjunath, Goutham B.
dc.contributor.author Yarlagadda, Venkateswarlu
dc.contributor.author Kaviyil, Jyothi E.
dc.contributor.author Ravikumar, Raju
dc.contributor.author Paramanandham, Krishnamoorthy
dc.contributor.author Shome, Bibek R.
dc.contributor.author Haldar, Jayanta
dc.date.accessioned 2017-01-04T09:09:01Z
dc.date.available 2017-01-04T09:09:01Z
dc.date.issued 2015
dc.identifier.citation PLoS One en_US
dc.identifier.citation 10 en_US
dc.identifier.citation 3 en_US
dc.identifier.citation 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. en_US
dc.identifier.issn 1932-6203
dc.identifier.uri https://libjncir.jncasr.ac.in/xmlui/10572/2013
dc.description Restricted access en_US
dc.description.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. en_US
dc.description.uri http://dx.doi.org/10.1371/journal.pone.0119422 en_US
dc.language.iso English en_US
dc.publisher Public Library Science en_US
dc.rights ?Public Library Science, 2015 en_US
dc.subject Multidisciplinary Sciences en_US
dc.subject Escherichia-Coli en_US
dc.subject Acinetobacter-Baumannii en_US
dc.subject Klebsiella-Pneumoniae en_US
dc.subject Resistance en_US
dc.subject Bacteria en_US
dc.subject Polymers en_US
dc.subject Mechanisms en_US
dc.subject Design en_US
dc.subject Agents en_US
dc.title Membrane-Active Macromolecules Resensitize NDM-1 Gram-Negative Clinical Isolates to Tetracycline Antibiotics en_US
dc.type Article en_US


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