title: Aryl-Alkyl-Lysines: Agents That Kill Planktonic Cells, Persister Cells, Biofilms of MRSA and Protect Mice from Skin-Infection.
abstract: 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.
authors.affiliation: Chemical Biology and Medicinal Chemistry Laboratory, New Chemistry Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bengaluru, 560064, Karnataka, India.
authors.forename: Chandradhish
authors.initials: C
authors.lastname: Ghosh
authors.affiliation: Chemical Biology and Medicinal Chemistry Laboratory, New Chemistry Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bengaluru, 560064, Karnataka, India.
authors.forename: Goutham B
authors.initials: GB
authors.lastname: Manjunath
authors.affiliation: Chemical Biology and Medicinal Chemistry Laboratory, New Chemistry Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bengaluru, 560064, Karnataka, India.
authors.forename: Mohini M
authors.initials: MM
authors.lastname: Konai
authors.affiliation: Chemical Biology and Medicinal Chemistry Laboratory, New Chemistry Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bengaluru, 560064, Karnataka, India.
authors.forename: Divakara S S M
authors.initials: DS
authors.lastname: Uppu
authors.affiliation: Chemical Biology and Medicinal Chemistry Laboratory, New Chemistry Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bengaluru, 560064, Karnataka, India.
authors.forename: Jiaul
authors.initials: J
authors.lastname: Hoque
authors.affiliation: National Institute of Veterinary Epidemiology and Disease Informatics (NIVEDI) Ramagondanahalli, Yelahanka, Bengaluru, Karnataka, 560064, India.
authors.forename: Krishnamoorthy
authors.initials: K
authors.lastname: Paramanandham
authors.affiliation: National Institute of Veterinary Epidemiology and Disease Informatics (NIVEDI) Ramagondanahalli, Yelahanka, Bengaluru, Karnataka, 560064, India.
authors.forename: Bibek R
authors.initials: BR
authors.lastname: Shome
authors.affiliation: Chemical Biology and Medicinal Chemistry Laboratory, New Chemistry Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bengaluru, 560064, Karnataka, India.
authors.forename: Jayanta
authors.initials: J
authors.lastname: Haldar
mesh_terms: D000478:Alkylation; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D018441:Biofilms / Q000187:drug effects*; D020405:Dermis / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D007700:Kinetics; D008239:Lysine / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D050296:Microbial Viability / Q000187:drug effects; D010933:Plankton / Q000166:cytology* / Q000187:drug effects; D012874:Skin Diseases, Infectious / Q000382:microbiology / Q000517:prevention & control*
chemical_list: D000900:Anti-Bacterial Agents; D008239:Lysine