Journal
PEPTIDES
Volume 82, Issue -, Pages 60-66Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.peptides.2016.05.010
Keywords
Antimicrobial peptide; Hybrid peptide; LPS-binding and -neutralizing activities; Gram-negative bacteria selectivity
Funding
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Science, ICT & Future Planning [NRF-2014R1A2A1A11050944]
- Intelligent Synthetic Biology Center of Global Frontier Project funded by the Ministry of Science, ICT & Future Planning [NRF-2013M3A6A8073556]
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Antimicrobial peptides (AMPs) provide a potential source of new antimicrobial therapeutics for the treatment of multidrug-resistant pathogens. To develop Gram-negative selective AMPs that can inhibit the effects of lipopolysaccharide (LPS)-induced sepsis, we added various rationally designed LPS-targeting peptides [amino acids 28-34 of lactoferrin (Lf28-34), amino acids 84-99 of bactericidal/permeability increasing protein (BPI84-99), and de novo peptide (Syn)] to the potent AMP, GNU7 (RLLRPLLQLLKQKLR). Compared to our original starting peptide GNU7, hybrid peptides had an 8- to 32-fold improvement in antimicrobial activity against Gram-negative bacteria, such as Escherichia coli and Salmonella typhimurium. Among them, Syn-GNU7 showed the strongest LPS-binding and -neutralizing activities, thus allowing it to selectively eliminate Gram-negative bacteria from within mixed cultures. Our results suggest that LPS-targeting peptides would be useful to increase the antimicrobial activity and selectivity of other AMPs against Gram-negative bacteria. (C) 2016 Elsevier Inc. All rights reserved.
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