Membrane-active macromolecules resensitize NDM-1 gram negative clinical isolates to tetracycline antibiotics
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Title |
Membrane-active macromolecules resensitize NDM-1 gram negative clinical isolates to tetracycline antibiotics
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Creator |
Divakara SSSU, Goutham BM, Venkateswarlu Y, Jyothi EK, Raju R, Krishnamoorthy P, Shome BR and Haldar J
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Subject |
Macromolecules, antibiotics, NDM-1
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Description |
Not Available
Gram-negative ‘superbugs’ such as New Delhi metallo-beta-lactamase-1 (blaNDM-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. This work was supported by the grant “Ramanujan fellowship” [SR/S2/RJN - 43/2009] from the Department of Science and Technology (DST), Govt. of India. |
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Date |
2018-09-19T04:51:50Z
2018-09-19T04:51:50Z 2015-03-19 |
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Type |
Research Paper
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Identifier |
Uppu DSSM, Manjunath GB, Yarlagadda V, Kaviyil JE, Ravikumar R, Paramanandham K, et al. (2015) Membrane-Active Macromolecules Resensitize NDM-1 Gram-Negative Clinical Isolates to Tetracycline Antibiotics. PLoS ONE 10(3): e0119422. doi:10.1371/journal.pone.0119422
1932-6203 http://krishi.icar.gov.in/jspui/handle/123456789/6990 |
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Language |
English
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Relation |
Not Available;
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Publisher |
Public Library of Science (PLoS)
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