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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
Not Available
 
Creator Divakara SSSU, Goutham BM, Venkateswarlu Y, Jyothi EK, Raju R, Krishnamoorthy P, Shome BR and Haldar J
 
Subject Macromolecules, antibiotics, NDM-1
 
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.
 
Date 2018-09-19T04:51:50Z
2018-09-19T04:51:50Z
2015-03-19
 
Type Research Paper
 
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
 
Language English
 
Relation Not Available;
 
Publisher Public Library of Science (PLoS)