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Comparison of the antibacterial effects of a short cationic peptide and 1% silver bioactive glass against extensively drug-resistant bacteria, Pseudomonas aeruginosa and Acinetobacter baumannii, isolated from burn patients

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Abstract

We have already established that a short cationic peptide (CM11) has high antimicrobial activity against a number of bacterial pathogens. Considering the untreatable problem of burn infections caused by Pseudomonas aeruginosa and Acinetobacter baumannii, this study evaluated and compared antibacterial effects of the CM11 peptide and 1% silver-doped bioactive glass (AgBG) against extensively drug-resistant strains of these bacteria which were isolated from burn patients. Accordingly, the bacteria were isolated from burn patients and their antibiotic resistance patterns and mechanisms were fully determined. The isolated bacterial from patients were resistant to almost all commonly used antibiotics and silver treatment. The isolates acquired their resistance through inactivation of their porin, the overexpression of efflux pump, and beta-lactamase. CM11 peptide and 1% AgBG had minimum inhibitory concentration (MIC) of ≥ 16 μg ml−1 and ≥ 4 mg ml−1 for clinical isolates, respectively. The minimum bactericidal concentration (MBC) of peptide and 1% AgBG for resistant bacteria was ≥ 32 μg ml−1 and ≥ 4 mg ml−1, respectively. Among the clinical isolates, two P. aeruginosa isolates and one A. baumannii isolate were resistant to 1% AgBG disk. The CM11 peptide also showed high biocompatibility in vivo and no cytotoxicity against fibroblasts and adipose-derived mesenchymal stem cells in concentrations ≤ 64 μg ml−1 and ≤ 32 μg ml−1, respectively, while the safe concentration of 1% AgBG for these cells was ≤ 16 μg ml−1. In conclusion, these findings indicated that the 1% silver is not safe and effective for treatment of such infections. The data suggest that CM11 peptide therapy is a reliable and safe strategy that can be used for the treatment of burn infections caused by antimicrobial-resistant isolates. The next stage of the study will be a multicenter clinical trial.

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Acknowledgements

We wish to express our appreciation to Dr. Ali Rostami for his constructive comments on this manuscript.

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Authors and Affiliations

  1. Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran

    Mehrdad Moosazadeh Moghaddam

  2. Department of Biotechnology, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Mohamad Eftekhary & Behrouz Farhadihosseinabadi

  3. Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Soroor Erfanimanesh

  4. Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, 19857-17443, Iran

    Ali Hashemi

  5. Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Mohamad Eftekhary, Vahid Fallah Omrani & Behrouz Farhadihosseinabadi

  6. Department of Parasitology and Mycology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Zohreh Lasjerdi

  7. Sarem Cell Research Center (SCRC), Sarem Women’s Hospital, Tehran, Iran

    Majid Mossahebi-Mohammadi

  8. Department of Chemistry, Bhupal Nobles University, Udaipur, Rajasthan, India

    Narendra Pal Singh Chauhan

  9. Nanotechnology and Regenerative Medicine Commercialization Centre (Ltd), The London Bioscience Innovation Centre, London, NW1 0NH, UK

    Alexander M. Seifalian

  10. Cellular and Molecular Research Centre, Iran University of Medical Sciences, Tehran, Iran

    Mazaher Gholipourmalekabadi

  11. Department of Tissue Engineering & Regenerative Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, 144961-4535, Iran

    Mazaher Gholipourmalekabadi

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  1. Mehrdad Moosazadeh Moghaddam
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  2. Mohamad Eftekhary
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  10. Alexander M. Seifalian
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  11. Mazaher Gholipourmalekabadi
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Contributions

MMM, AH and MG conceived and designed the study. MMM, ME, BF, ZL, VFO, MG, MM-M, AH and MMM performed the experiments. MG, SE, AH and HG analyzed the data. MG and AH interpreted the results. MG, SE, MMM, ME, BF and AH prepared the manuscript. MG, AMS, SE, NPS, AH and MMM reviewed the preparation of manuscript.

Corresponding authors

Correspondence to Ali Hashemi or Mazaher Gholipourmalekabadi.

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Conflict of interest

The authors declare that there is no conflict of interest regarding the publication of this article.

Ethical approval

The studies have been approved by the research ethics committee of the Shahid Beheshti University of Medical Sciences, Tehran, Iran. All procedures performed in studies involving human participants were in accordance with the ethical standards of the SBUMS research committee and have been performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. Also for animal studies, experiments were approved by the Institutional Animal Care and Use committee of the SBUMS, and were performed in accordance with the Guide for the Care and Use of Laboratory Animals published by the National Institutes of Health.

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For this type of study, formal consent is not required.

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Handling Editor: F. Albericio.

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Supplementary material 1 (DOCX 1472 kb)

726_2018_2638_MOESM2_ESM.tif

(A) Analysis of synthetic peptide (CM 11) by Reverse-phase HPLC using C18 Tracer column and a linear gradient from 10 to 60% acetonitrile in water with 0.1% TFA. (B) Mass spectroscopic analysis of the CM11 peptide (MH+=1415.85) was performed by electrospray ionization mass spectrometry which confirmed peptide identity. Supplementary material 2 (TIFF 804 kb)

726_2018_2638_MOESM3_ESM.tif

Characterization of hAT-MSCs. (A) The images taken from the hAT-MSCs under light microscope by days 3, 7 and 21 post-extraction, and the fibroblast L929. (B) Flow cytometric results of the hAT-MSCs. The percentages of the cells expressing Sca1, CD44, CD90 and CD105, CD11b, CD33, CD34 and CD45 were 98.5%, 97.9%, 98.4 and 96.5%, 2.9%, 3.1%, 2.6%, 4.3%, respectively. Supplementary material 3 (TIFF 5325 kb)

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Moosazadeh Moghaddam, M., Eftekhary, M., Erfanimanesh, S. et al. Comparison of the antibacterial effects of a short cationic peptide and 1% silver bioactive glass against extensively drug-resistant bacteria, Pseudomonas aeruginosa and Acinetobacter baumannii, isolated from burn patients. Amino Acids 50, 1617–1628 (2018). https://doi.org/10.1007/s00726-018-2638-z

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