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DC Field | Value | Language |
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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 |
Appears in Collections: | Research Papers (Jayanta Haldar) |
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