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Oral delivery of cholic acid-derived amphiphile helps in combating salmonella-mediated gut infection and inflammation

Yadav, Kavita and Kumar, Sandeep (2019) Oral delivery of cholic acid-derived amphiphile helps in combating salmonella-mediated gut infection and inflammation. Bioconjugate Chemistry, 30 (3). pp. 721-732. ISSN 1043-1802

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Abstract

A major impediment to develop effective antimicrobials against Gram-negative bacteria like Salmonella is the ability of the bacteria to develop resistance against existing antibiotics and inability of the antimicrobials to clear the intracellular bacteria residing in the gastrointestinal tract. As critical balance of charge and hydrophobicity is required for effective membrane-targeting antimicrobials without causing any toxicity to mammalian cells, herein we report the synthesis and antibacterial properties of Cholic Acid-derived amphiphiles conjugated with alkyl chains of varied hydrophobicity. Relative to other hydrophobic counterparts, compound with hexyl chain (6) acted as an effective antimicrobial against different Gramnegative bacteria. Apart from its ability to permeate the outer and inner membranes of bacteria; compound 6 can to cross the cellular and lysosomal barriers of epithelial cells and macrophages and kill the facultative intracellular bacteria without disrupting the mammalian cell membranes. Oral delivery of compound 6 was able to clear the Salmonella-mediated gutinfection and inflammation, and was able to combat persistent, stationary and multi-drug resistant clinical strains. Therefore, our study reveals the ability of Cholic Acid-derived amphiphile to clear intracellular bacteria and Salmonella-mediated gut infection and inflammation.

Item Type: Article
Subjects: Research > Research Center - Health Sciences
Depositing User: KMC Library
Date Deposited: 01 Apr 2019 03:59
Last Modified: 01 Apr 2019 03:59
URI: http://eprints.manipal.edu/id/eprint/153551

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