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Cytotoxicity and Antibacterial Effect of Trp-Substituted CM11 Cationic Peptide Against Drug-Resistant Isolates of Brucella melitensis Alone and in Combination with Recommended Antibiotics

  • Hoda Moravej
  • Mahdi Fasihi-Ramandi
  • Mehrdad Moosazadeh Moghaddam
  • Reza MirnejadEmail author
Article

Abstract

During the recent years, antibiotic resistance of pathogenic bacteria to conventional and common antibiotics has considered as a global concern. Therefore, researchers attend to find a new class of antimicrobial agents such as antimicrobial peptides (AMP), but some limitations are on the therapeutic use of AMPs such as cytotoxicity. To overcome these limitations various strategies have been described such as designing AMP analogues and/or combined use of them with synergistic effects. According to the many studies substitution of tryptophan as an amino acid residue with negative hydropathy index (− 0.9) to the leucine residue that is an amino acid with high positive hydropathy index (3.8) can enhance bactericidal activity and reduce cytotoxicity. Based on this topic in this study, a peptide modification was done by substitution of tryptophan at position 3 (leucine amino acid) of the CM11 antimicrobial peptide to promote its antibacterial activity and decrease cytotoxicity effect on eukaryotic cells. In the following, we investigated peptide antibacterial activity alone and in combination with common antibiotics against drug-resistant isolates of Brucella melitensis. Specific antibiotics were selected considering the CLSI guideline and peptide-antibiotics synergistic effect was done by checkerboard procedure through the broth microdilution method. In comparison with the CM11 peptide, modified peptide exhibited similar antimicrobial activity against clinical isolates of antibiotic-resistant B. melitensis with a reduction in hemolytic and cytotoxicity activates. Also, the synergistic effect between modified peptide and streptomycin and rifampin was observed as synergy and additive, respectively.

Keywords

Brucella melitensis Antibiotic resistance Antimicrobial peptide Synergistic effect Amino acid substitution 

Notes

Acknowledgements

This study is extracted from a MSc thesis which was approved and supported by Molecular Biology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran. The authors would like to thank colleagues in this centre for their kind and generous assistance.

Compliance with Ethical Standards

Conflict of interest

The authors declare that there are no conflicts of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Hoda Moravej
    • 1
  • Mahdi Fasihi-Ramandi
    • 1
  • Mehrdad Moosazadeh Moghaddam
    • 2
  • Reza Mirnejad
    • 1
    Email author
  1. 1.Molecular Biology Research Center, Systems Biology and Poisoning InstituteBaqiyatallah University of Medical SciencesTehranIran
  2. 2.Applied Biotechnology Research CenterBaqiyatallah University of Medical SciencesTehranIran

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