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Integrated evolutionary analysis reveals antimicrobial peptides with limited resistance

Author

Listed:
  • Réka Spohn

    (Institute of Biochemistry, Biological Research Centre)

  • Lejla Daruka

    (Institute of Biochemistry, Biological Research Centre
    University of Szeged)

  • Viktória Lázár

    (Institute of Biochemistry, Biological Research Centre
    Technion - Israel Institute of Technology)

  • Ana Martins

    (Institute of Biochemistry, Biological Research Centre)

  • Fanni Vidovics

    (Institute of Biochemistry, Biological Research Centre)

  • Gábor Grézal

    (Institute of Biochemistry, Biological Research Centre
    HCEMM-BRC Metabolic Systems Biology Lab)

  • Orsolya Méhi

    (Institute of Biochemistry, Biological Research Centre)

  • Bálint Kintses

    (Institute of Biochemistry, Biological Research Centre
    University of Szeged)

  • Mónika Számel

    (Institute of Biochemistry, Biological Research Centre
    University of Szeged)

  • Pramod K. Jangir

    (Institute of Biochemistry, Biological Research Centre
    University of Szeged)

  • Bálint Csörgő

    (Institute of Biochemistry, Biological Research Centre
    University of California, San Francisco, Department of Microbiology and Immunology)

  • Ádám Györkei

    (Institute of Biochemistry, Biological Research Centre
    HCEMM-BRC Metabolic Systems Biology Lab)

  • Zoltán Bódi

    (Institute of Biochemistry, Biological Research Centre)

  • Anikó Faragó

    (University of Szeged
    University of Szeged)

  • László Bodai

    (University of Szeged)

  • Imre Földesi

    (University of Szeged)

  • Diána Kata

    (University of Szeged)

  • Gergely Maróti

    (Hungarian Academy of Sciences)

  • Bernadett Pap

    (Hungarian Academy of Sciences)

  • Roland Wirth

    (University of Szeged)

  • Balázs Papp

    (Institute of Biochemistry, Biological Research Centre
    HCEMM-BRC Metabolic Systems Biology Lab)

  • Csaba Pál

    (Institute of Biochemistry, Biological Research Centre)

Abstract

Antimicrobial peptides (AMPs) are promising antimicrobials, however, the potential of bacterial resistance is a major concern. Here we systematically study the evolution of resistance to 14 chemically diverse AMPs and 12 antibiotics in Escherichia coli. Our work indicates that evolution of resistance against certain AMPs, such as tachyplesin II and cecropin P1, is limited. Resistance level provided by point mutations and gene amplification is very low and antibiotic-resistant bacteria display no cross-resistance to these AMPs. Moreover, genomic fragments derived from a wide range of soil bacteria confer no detectable resistance against these AMPs when introduced into native host bacteria on plasmids. We have found that simple physicochemical features dictate bacterial propensity to evolve resistance against AMPs. Our work could serve as a promising source for the development of new AMP-based therapeutics less prone to resistance, a feature necessary to avoid any possible interference with our innate immune system.

Suggested Citation

  • Réka Spohn & Lejla Daruka & Viktória Lázár & Ana Martins & Fanni Vidovics & Gábor Grézal & Orsolya Méhi & Bálint Kintses & Mónika Számel & Pramod K. Jangir & Bálint Csörgő & Ádám Györkei & Zoltán Bódi, 2019. "Integrated evolutionary analysis reveals antimicrobial peptides with limited resistance," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12364-6
    DOI: 10.1038/s41467-019-12364-6
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