The Design and Functional Characterization of the Antimicrobial and Antibiofilm Activities of BMAP27-Melittin, a Rationally Designed Hybrid Peptide

作者: Ammar Almaaytah , Shadi Tarazi , Mohammad Al-Fandi , Ahmad Abuilhaija , Nizar Al-shar’i

DOI: 10.1007/S10989-014-9444-6

关键词: Rational designMelittinMultiple drug resistanceMicrobiologyAntimicrobialTherapeutic indexBiologyAntibioticsAntimicrobial peptidesPeptide

摘要: BMAP-27 and melittin are two antimicrobial peptides (AMPs) that display potent activities against a wide range of microbes including multidrug resistant (MDR) strains bacteria. Unfortunately, their significant toxicity eukaryotic cells has hampered development into clinically useful antibiotics. In this study, we have rationally designed novel hybrid AMP aiming to retain the while enhancing therapeutic index. The strategy employed in our design was based on combining individual α-helical fragments each generate with improved characteristics compared parent peptides. Named as BMAP27-Melittin, peptide displayed broad spectrum activity standard representative Gram-positive Gram-negative bacterial 1–7.5 µM. Moreover, managed kill MDR bacteria potency MIC values low 1 BMAP27-Melittin also proved exhibit antibiofilm hemolytic antiproliferative studies revealed is exhibiting minimal at concentrations. Additionally, molecular dynamics simulations folding folded well-defined structure; supporting experimental findings. Overall, work highlights potential rational generating AMPs enhanced specificity could be developed successful therapeutics for treatment infections.

参考文章(37)
Howard Ceri, Douglas W. Morck, Ronald R. Read, Merle E. Olson, Andre G. Buret, Biofilm bacteria: formation and comparative susceptibility to antibiotics Canadian Journal of Veterinary Research-revue Canadienne De Recherche Veterinaire. ,vol. 66, pp. 86- 92 ,(2002)
Howard Ceri, Merle Olson, Douglas Morck, Douglas Storey, Ronald Read, Andre Buret, Barbara Olson, [25] The MBEC assay system: Multiple equivalent biofilms for antibiotic and biocide susceptibility testing Methods in Enzymology. ,vol. 337, pp. 377- 385 ,(2001) , 10.1016/S0076-6879(01)37026-X
Jochen Wiesner, Andreas Vilcinskas, Antimicrobial peptides: The ancient arm of the human immune system Virulence. ,vol. 1, pp. 440- 464 ,(2010) , 10.4161/VIRU.1.5.12983
Wei Wang, Rui Tao, Zhongchun Tong, Yonglin Ding, Rong Kuang, Shafei Zhai, Jun Liu, Longxing Ni, Effect of a novel antimicrobial peptide chrysophsin-1 on oral pathogens and Streptococcus mutans biofilms. Peptides. ,vol. 33, pp. 212- 219 ,(2012) , 10.1016/J.PEPTIDES.2012.01.006
Yibing Huang, Jinfeng Huang, Yuxin Chen, None, Alpha-helical cationic antimicrobial peptides: relationships of structure and function Protein & Cell. ,vol. 1, pp. 143- 152 ,(2010) , 10.1007/S13238-010-0004-3
Kim A. Brogden, Antimicrobial peptides: pore formers or metabolic inhibitors in bacteria? Nature Reviews Microbiology. ,vol. 3, pp. 238- 250 ,(2005) , 10.1038/NRMICRO1098
Brian M. Peters, Mark E. Shirtliff, Mary Ann Jabra-Rizk, Antimicrobial Peptides: Primeval Molecules or Future Drugs? PLoS Pathogens. ,vol. 6, pp. e1001067- ,(2010) , 10.1371/JOURNAL.PPAT.1001067
A. Pompilio, M. Scocchi, S. Pomponio, F. Guida, A. Di Primio, E. Fiscarelli, R. Gennaro, G. Di Bonaventura, Antibacterial and anti-biofilm effects of cathelicidin peptides against pathogens isolated from cystic fibrosis patients Peptides. ,vol. 32, pp. 1807- 1814 ,(2011) , 10.1016/J.PEPTIDES.2011.08.002
David Andreu, Josep Ubach, Anita Boman, Birgitta Wåhlin, David Wade, R.B. Merrifield, Hans G. Boman, Shortened cecropin A-melittin hybrids. Significant size reduction retains potent antibiotic activity. FEBS Letters. ,vol. 296, pp. 190- 194 ,(1992) , 10.1016/0014-5793(92)80377-S