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Ghosh C.,Jawaharlal Nehru Centre for Advanced Scientific Research | Manjunath G.B.,Jawaharlal Nehru Centre for Advanced Scientific Research | Konai M.M.,Jawaharlal Nehru Centre for Advanced Scientific Research | Uppu D.S.S.M.,Jawaharlal Nehru Centre for Advanced Scientific Research | And 4 more authors.
ACS Infectious Diseases | Year: 2016

Infections caused by drug-resistant Gram-negative pathogens continue to be significant contributors to human morbidity. The recent advent of New Delhi metallo-β-lactamase-1 (blaNDM-1) producing pathogens, against which few drugs remain active, has aggravated the problem even further. This paper shows that aryl-alkyl-lysines, membrane-active small molecules, are effective in treating infections caused by Gram-negative pathogens. One of the compounds of the study was effective in killing planktonic cells as well as dispersing biofilms of Gram-negative pathogens. The compound was extremely effective in disrupting preformed biofilms and did not select resistant bacteria in multiple passages. The compound retained activity in different physiological conditions and did not induce any toxic effect in female Balb/c mice until concentrations of 17.5 mg/kg. In a murine model of Acinetobacter baumannii burn infection, the compound was able to bring the bacterial burden down significantly upon topical application for 7 days. © 2015 American Chemical Society. Source


Ghosh C.,Jawaharlal Nehru Centre for Advanced Scientific Research | Manjunath G.B.,Jawaharlal Nehru Centre for Advanced Scientific Research | Konai M.M.,Jawaharlal Nehru Centre for Advanced Scientific Research | Uppu D.S.S.M.,Jawaharlal Nehru Centre for Advanced Scientific Research | And 4 more authors.
PLoS ONE | Year: 2015

Development of synthetic strategies to combat Staphylococcal infections, especially those caused by methicillin resistant Staphyloccus aureus (MRSA), needs immediate attention. In this manuscript we report the ability of aryl-alkyl-lysines, simple membrane active small molecules, to treat infections caused by planktonic cells, persister cells and biofilms of MRSA. A representative compound, NCK-10, did not induce development of resistance in planktonic cells in multiple passages and retained activity in varying environments of pH and salinity. At low concentrations the compound was able to depolarize and permeabilize the membranes of S. aureus persister cells rapidly. Treatment with the compound not only eradicated pre-formed MRSA biofilms, but also brought down viable counts in bacterial biofilms. In a murine model of MRSA skin infection, the compound was more effective than fusidic acid in bringing down the bacterial burden. Overall, this class of molecules bears potential as antibacterial agents against skin-infections. © 2015 Ghosh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Source

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