Correction: Membrane-active macromolecules resensitize NDM-1 gram-negative clinical isolates to tetracycline antibiotics

• Published in: PloS one 2015-04, Vol.10 (4), p.e0126757
• Main Authors: Uppu, Divakara S S M, Manjunath, Goutham B, Yarlagadda, Venkateswarlu, Kaviyil, Jyothi E, Ravikumar, Raju, Paramanandham, Krishnamoorthy, Shome, Bibek R, Haldar, Jayanta
• Format: Article
• Language: English
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0126757

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 tetracyclinein 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.