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 |