Enhancement of the antimicrobial activity and selectivity of GNU7 against Gram-negative bacteria by fusion with LPS-targeting peptide |
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| Institution: | 1. Division of Life Science, Gyeongsang National University, Jinju 52828, South Korea;2. Research Institute of Life Science, Gyeongsang National University, Jinju 52828, South Korea;3. Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, South Korea;1. Department of Internal Medicine, Division of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, Saint Louis, MO 63110, United States;2. Department of Internal Medicine, Divsion of Biostatistics, Washington University School of Medicine, Saint Louis, MO 63110, United States;3. Department of Internal Medicine, Division of Nutritional Science, Washington University School of Medicine, Saint Louis, MO 63110, United States;1. Department of Periodontology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China;2. Central Laboratory of Stomatology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China;3. Department of Orthodontics, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, China;1. Laboratory of Cardiovascular Medicine, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan;2. Department of Endocrinology, Diabetes and Metabolism, Kitasato University School of Medicine, Sagamihara, Japan;1. Cátedra Histología y Embriología Animal, Facultad de Ciencias Naturales y Museo, Universidad Nacional de La Plata (FCNyM-UNLP), La Plata, Argentina;2. Centro de Investigación Sobre Enfermedades Infecciosas – Instituto Nacional de Salud Pública (CISEI-INSP), Cuernavaca, Mexico;3. Consejo Nacional de Investigaciones Científicas y Técnicas, Argentina;1. Molecular Biology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran;2. Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran;3. Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran;1. Research Institute of Life Science, Gyeongsang National University, Jinju, 52828, South Korea;2. Division of Life Science, Gyeongsang National University, Jinju, 52828, South Korea |
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| Abstract: | 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. |
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| Keywords: | Antimicrobial peptide Hybrid peptide LPS-binding and -neutralizing activities Gram-negative bacteria selectivity |
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