DSpace Repository

Lysine-Based Small Molecules That Disrupt Biofilms and Kill both Actively Growing Planktonic and Nondividing Stationary Phase Bacteria

Show simple item record

dc.contributor.author Konai, Mohini M.
dc.contributor.author Haldar, Jayanta
dc.date.accessioned 2017-01-04T09:09:00Z
dc.date.available 2017-01-04T09:09:00Z
dc.date.issued 2015
dc.identifier.citation ACS Infectious Diseases en_US
dc.identifier.citation 1 en_US
dc.identifier.citation 10 en_US
dc.identifier.citation 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. en_US
dc.identifier.issn 2373-8227
dc.identifier.uri https://libjncir.jncasr.ac.in/xmlui/10572/2007
dc.description Restricted access en_US
dc.description.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. en_US
dc.description.uri http://dx.doi.org/10.1021/acsinfecdis.5b00056 en_US
dc.language.iso English en_US
dc.publisher American Chemical Society en_US
dc.rights ?American Chemical Society, 2015 en_US
dc.subject Medicinal Chemistry en_US
dc.subject Infectious Diseases en_US
dc.subject bacterial resistance en_US
dc.subject antibacterial en_US
dc.subject anti-biofilm en_US
dc.subject stationary phase en_US
dc.subject lysine en_US
dc.subject Pseudomonas-Aeruginosa en_US
dc.subject Antimicrobial Peptides en_US
dc.subject Antibiotic-Resistance en_US
dc.subject Antibacterial Agents en_US
dc.subject Infectious-Diseases en_US
dc.subject Peptoid Mimics en_US
dc.subject Polymers en_US
dc.subject Lipopeptides en_US
dc.subject Derivatives en_US
dc.subject Foldamers en_US
dc.title Lysine-Based Small Molecules That Disrupt Biofilms and Kill both Actively Growing Planktonic and Nondividing Stationary Phase Bacteria en_US
dc.type Article en_US


Files in this item

This item appears in the following Collection(s)

Show simple item record

Search DSpace


Advanced Search

Browse

My Account