A potent antibacterial activity of new short d-enantiomeric lipopeptide against multi drug resistant bacteria |
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Authors: | Jaeho Lee Shanghyeon Kim Ji-Yeong Sim Daeun Lee Ha Hyung Kim Jae Sam Hwang Dong Gun Lee Zee-Yong Park Jae Il Kim |
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Institution: | 1. School of Life Sciences, Gwangju Institute of Science and Technology, 123, Cheomdangwagi-ro, Buk-gu, Gwangju 61005, Republic of Korea;2. Biotherapeutics and Glycomics Laboratory, College of Pharmacy, Chung-Ang University, 84, Heukseok-ro, Dongjak-gu, Seoul 06974, Republic of Korea;3. Department of Agricultural Biology, National Academy of Agricultural Science, RDA, 166, Nongsaengmyeong-ro, Iseo-myeon, Wanju_Gun, Jeollabuk-do 55365, Republic of Korea;4. School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, College of National Sciences, Kyungpook National University, 80 Daehakro, Bukgu, Daegu 41566, Republic of Korea |
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Abstract: | The emergence of drug-resistant pathogenic bacteria threatens human health. Resistance to existing antibiotics is increasing, while the emergence of new antibiotics is slowing. Cationic antimicrobial peptides (CAMPs) are fascinating alternative antibiotics because they possess a broad spectrum of activity, being active against both Gram-positive and Gram-negative bacteria including those resistant to traditional antibiotics. However, low bioavailability resulting from enzymatic degradation and attenuation by divalent cations like Mg2+ and Ca2+ limits their use as antibiotic agents. Here, we report the design of new CAMPs showing both high antibacterial activity and serum stability under physiological ion concentrations. The peptides were designed by applying two approaches, the use of d-enantiomer and lipidation. Based on the sequence of the CopW (LLWIALRKK-NH2), a nonapeptide derived from coprisin, a series of novel d-form CopW lipopeptides with different acyl chain lengths (C6, C8, C10, C12, C14, and C16) were synthesized and evaluated with respect to their activity and salt sensitivity. Among the analogs, the d-form lipopeptide dCopW3 exhibited MIC values ranging from 1.25 to 5?μM against multidrug-resistant bacteria. Significantly, this compound did not induce bacterial resistance and was highly stable in human serum proteases. The results emphasize the potential of cationic d-form lipopeptide as therapeutically valuable antibiotics for treating drug-resistant bacterial infections. |
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Keywords: | ATCC American Type Culture Collection BSA bovine serum albumin CAMHB cations adjusted Mueller Hinton broth CAMP cationic antimicrobial peptide CCARM Culture Collection of Antibiotic-Resistant Microbe CDC Centers for Disease Control and Prevention ELISA Enzyme-linked Immunosorbent Assay FE-SEM field emission scanning electron microscopy hRBCs human red blood cells KCCM Korean Culture Center of Microorganisms KCTC Korean Collection for Type Cultures MDR multidrug-resistant MIC minimum inhibitory concentration MRSA VRE Cationic antimicrobial peptides Coprisin Coprisin analog Fatty acid conjugation |
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