Please use this identifier to cite or link to this item: http://lib.jncasr.ac.in:8080/jspui/handle/10572/2007
Title: Lysine-Based Small Molecules That Disrupt Biofilms and Kill both Actively Growing Planktonic and Nondividing Stationary Phase Bacteria
Authors: Konai, Mohini M.
Haldar, Jayanta
Keywords: Medicinal Chemistry
Infectious Diseases
bacterial resistance
antibacterial
anti-biofilm
stationary phase
lysine
Pseudomonas-Aeruginosa
Antimicrobial Peptides
Antibiotic-Resistance
Antibacterial Agents
Infectious-Diseases
Peptoid Mimics
Polymers
Lipopeptides
Derivatives
Foldamers
Issue Date: 2015
Publisher: American Chemical Society
Citation: ACS Infectious Diseases
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Konai, M. M.; Haldar, J., Lysine-Based Small Molecules That Disrupt Biofilms and Kill both Actively Growing Planktonic and Nondividing Stationary Phase Bacteria. ACS Infectious Diseases 2015, 1 (10), 469-478.
Abstract: The emergence of bacterial resistance is a major threat to global health. Alongside this issue, formation of bacterial biofilms is another cause of concern because most antibiotics are ineffective against these recalcitrant microbial communities. Ideal future antibacterial therapeutics should possess both antibacterial and anti-biofilm activities. In this study we engineered lysine-based small molecules, which showed not only commendable broad-spectrum antibacterial activity but also potent biofilm-disrupting properties. Synthesis of these lipophilic lysine-norspermidine conjugates was achieved in three simple reaction steps, and the resultant molecules displayed potent antibacterial activity against various Gram-positive (Staphylococcus aureus, Enterococcus faecium) and Gram-negative bacteria (Escherichia coli) including drug-resistant superbugs MRSA (methicillin-resistant S. aureus), VRE (vancomycin-resistant E. faecium), and beta-lactam-resistant Klebsiella pneumoniae. An optimized compound in the series showed activity against planktonic bacteria in the concentration range of 3-10 mu g/mL, and bactericidal activity against stationary phase S. aureus was observed within an hour. The compound also displayed about 120 fold selectivity toward both classes of bacteria (S. aureus and E coli) over human erythrocytes. This rapidly bactericidal compound primarily acts on bacteria by causing significant membrane depolarization and K+ leakage. Most importantly, the compound disrupted preformed biofilms of S. aureus and did not trigger bacterial resistance. Therefore, this class of compounds has high potential to be developed as future antibacterial drugs for treating infections caused by planktonic bacteria as well as bacterial biofilms.
Description: Restricted access
URI: http://hdl.handle.net/10572/2007
ISSN: 2373-8227
Appears in Collections:Research Papers (Jayanta Haldar)

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