Novel Hybrid Peptide Cecropin A (1-8)-LL37 (17-30) with Potential Antibacterial Activity

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2016 Jul 2

PMID 27367675

Citations 24

Authors

Xu-Biao Wei

Ru-Juan Wu

Da-Yong Si

Xiu-Dong Liao

Lu-Lu Zhang

Ri-Jun Zhang

Affiliations

Soon will be listed here.

Abstract

Hybridizing different antimicrobial peptides (AMPs) is a particularly successful approach to obtain novel AMPs with increased antimicrobial activity but minimized cytotoxicity. The hybrid peptide cecropin A (1-8)-LL37 (17-30) (C-L) combining the hydrophobic N-terminal fragment of cecropin A (C) with the core antimicrobial fragment of LL37 (L) was designed and synthesized. C-L showed higher antibacterial activity against all indicator strains than C and L, and no hemolytic activity to sheep erythrocytes was observed. C-L kills bacterial cells and causes disruption of surface structure, as determined by scanning electron microscopy. Synergistic effects were observed in the combination of C-L with several antibiotics (chloramphenicol, thiamphenicol, or neomycin sulfate) against Escherichia coli and Staphylococcus aureus.

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References

Bonucci A, Balducci E, Pistolesi S, Pogni R . The defensin-lipid interaction: insights on the binding states of the human antimicrobial peptide HNP-1 to model bacterial membranes. Biochim Biophys Acta. 2012; 1828(2):758-64. DOI: 10.1016/j.bbamem.2012.11.011. View

Splith K, Neundorf I . Antimicrobial peptides with cell-penetrating peptide properties and vice versa. Eur Biophys J. 2011; 40(4):387-97. DOI: 10.1007/s00249-011-0682-7. View

Pavon N, Buelna-Chontal M, Hernandez-Esquivel L, Hernandez S, Chavez E, Conde R . Mitochondrial inactivation by Anopheles albimanus cecropin 3: molecular mechanisms. Peptides. 2013; 53:202-9. DOI: 10.1016/j.peptides.2013.07.010. View

Christensen B, Fink J, MERRIFIELD R, Mauzerall D . Channel-forming properties of cecropins and related model compounds incorporated into planar lipid membranes. Proc Natl Acad Sci U S A. 1988; 85(14):5072-6. PMC: 281690. DOI: 10.1073/pnas.85.14.5072. View

Dosler S, Alev Gerceker A . In vitro activities of nisin alone or in combination with vancomycin and ciprofloxacin against methicillin-resistant and methicillin-susceptible Staphylococcus aureus strains. Chemotherapy. 2012; 57(6):511-6. DOI: 10.1159/000335598. View

Dennison S, Wallace J, Harris F, Phoenix D . Amphiphilic alpha-helical antimicrobial peptides and their structure/function relationships. Protein Pept Lett. 2005; 12(1):31-9. DOI: 10.2174/0929866053406084. View

Durell S, Raghunathan G, Guy H . Modeling the ion channel structure of cecropin. Biophys J. 1992; 63(6):1623-31. PMC: 1262279. DOI: 10.1016/S0006-3495(92)81730-7. View

Prenner E, LEWIS R, McElhaney R . The interaction of the antimicrobial peptide gramicidin S with lipid bilayer model and biological membranes. Biochim Biophys Acta. 1999; 1462(1-2):201-21. DOI: 10.1016/s0005-2736(99)00207-2. View

Brown K, Hancock R . Cationic host defense (antimicrobial) peptides. Curr Opin Immunol. 2005; 18(1):24-30. DOI: 10.1016/j.coi.2005.11.004. View

10.

Marassi F, Opella S, Juvvadi P, MERRIFIELD R . Orientation of cecropin A helices in phospholipid bilayers determined by solid-state NMR spectroscopy. Biophys J. 1999; 77(6):3152-5. PMC: 1300585. DOI: 10.1016/S0006-3495(99)77145-6. View

11.

Hao G, Shi Y, Han J, Li Q, Tang Y, Le G . Design and analysis of structure-activity relationship of novel antimicrobial peptides derived from the conserved sequence of cecropin. J Pept Sci. 2007; 14(3):290-8. DOI: 10.1002/psc.926. View

12.

Lu X, Jin X, Zhu J, Mei H, Ma Y, Chu F . Expression of the antimicrobial peptide cecropin fused with human lysozyme in Escherichia coli. Appl Microbiol Biotechnol. 2010; 87(6):2169-76. DOI: 10.1007/s00253-010-2606-3. View

13.

Lin M, Hui C, Chen J, Wu J . Truncated antimicrobial peptides from marine organisms retain anticancer activity and antibacterial activity against multidrug-resistant Staphylococcus aureus. Peptides. 2013; 44:139-48. DOI: 10.1016/j.peptides.2013.04.004. View

14.

Lewis K . Platforms for antibiotic discovery. Nat Rev Drug Discov. 2013; 12(5):371-87. DOI: 10.1038/nrd3975. View

15.

Moraes L, Fazio M, Vieira R, Nakaie C, Miranda M, Schreier S . Conformational and functional studies of gomesin analogues by CD, EPR and fluorescence spectroscopies. Biochim Biophys Acta. 2006; 1768(1):52-8. DOI: 10.1016/j.bbamem.2006.08.016. View

16.

Li X, Li Y, Han H, Miller D, Wang G . Solution structures of human LL-37 fragments and NMR-based identification of a minimal membrane-targeting antimicrobial and anticancer region. J Am Chem Soc. 2006; 128(17):5776-85. DOI: 10.1021/ja0584875. View

17.

Epand R, Vogel H . Diversity of antimicrobial peptides and their mechanisms of action. Biochim Biophys Acta. 1999; 1462(1-2):11-28. DOI: 10.1016/s0005-2736(99)00198-4. View

18.

Dosler S, Mataraci E . In vitro pharmacokinetics of antimicrobial cationic peptides alone and in combination with antibiotics against methicillin resistant Staphylococcus aureus biofilms. Peptides. 2013; 49:53-8. DOI: 10.1016/j.peptides.2013.08.008. View

19.

Sato H, Feix J . Peptide-membrane interactions and mechanisms of membrane destruction by amphipathic alpha-helical antimicrobial peptides. Biochim Biophys Acta. 2006; 1758(9):1245-56. DOI: 10.1016/j.bbamem.2006.02.021. View

20.

Gronberg A, Zettergren L, Agren M . Stability of the cathelicidin peptide LL-37 in a non-healing wound environment. Acta Derm Venereol. 2011; 91(5):511-5. DOI: 10.2340/00015555-1102. View