PMID- 25879927 OWN - NLM STAT- MEDLINE DCOM- 20160419 LR - 20201209 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 10 IP - 4 DP - 2015 TI - Correction: Membrane-active macromolecules resensitize NDM-1 gram-negative clinical isolates to tetracycline antibiotics. PG - e0126757 LID - 10.1371/journal.pone.0126757 [doi] LID - e0126757 AB - 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. FAU - Uppu, Divakara S S M AU - Uppu DS FAU - Manjunath, Goutham B AU - Manjunath GB FAU - Yarlagadda, Venkateswarlu AU - Yarlagadda V FAU - Kaviyil, Jyothi E AU - Kaviyil JE FAU - Ravikumar, Raju AU - Ravikumar R FAU - Paramanandham, Krishnamoorthy AU - Paramanandham K FAU - Shome, Bibek R AU - Shome BR FAU - Haldar, Jayanta AU - Haldar J LA - eng PT - Journal Article PT - Published Erratum PT - Research Support, Non-U.S. Gov't DEP - 20150416 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Anti-Bacterial Agents) RN - EC 3.5.2.6 (beta-Lactamases) RN - EC 3.5.2.6 (beta-lactamase NDM-1) RN - F8VB5M810T (Tetracycline) SB - IM EFR - PLoS One. 2015;10(3):e0119422. PMID: 25789871 MH - Animals MH - Anti-Bacterial Agents/administration & dosage MH - Cell Membrane/*metabolism MH - Drug Resistance, Bacterial/*drug effects MH - Escherichia coli/drug effects/isolation & purification MH - Escherichia coli Infections/*drug therapy/microbiology MH - Humans MH - Klebsiella Infections/*drug therapy/microbiology MH - Klebsiella pneumoniae/drug effects/isolation & purification MH - Mice MH - Tetracycline/*administration & dosage MH - beta-Lactamases/*metabolism PMC - PMC4400169 EDAT- 2015/04/17 06:00 MHDA- 2016/04/20 06:00 PMCR- 2015/04/16 CRDT- 2015/04/17 06:00 PHST- 2015/04/17 06:00 [entrez] PHST- 2015/04/17 06:00 [pubmed] PHST- 2016/04/20 06:00 [medline] PHST- 2015/04/16 00:00 [pmc-release] AID - PONE-D-15-15498 [pii] AID - 10.1371/journal.pone.0126757 [doi] PST - epublish SO - PLoS One. 2015 Apr 16;10(4):e0126757. doi: 10.1371/journal.pone.0126757. eCollection 2015.