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Chemical-genetic profiling reveals limited cross-resistance between antimicrobial peptides with different modes of action

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Listed:
  • Bálint Kintses

    (Institute of Biochemistry, Biological Research Centre
    HCEMM-BRC Translational Microbiology Lab
    University of Szeged)

  • Pramod K. Jangir

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

  • Gergely Fekete

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

  • Mónika Számel

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

  • Orsolya Méhi

    (Institute of Biochemistry, Biological Research Centre)

  • Réka Spohn

    (Institute of Biochemistry, Biological Research Centre)

  • Lejla Daruka

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

  • Ana Martins

    (Institute of Biochemistry, Biological Research Centre)

  • Ali Hosseinnia

    (University of Regina)

  • Alla Gagarinova

    (University of Saskatchewan)

  • Sunyoung Kim

    (University of Regina)

  • Sadhna Phanse

    (University of Regina)

  • Bálint Csörgő

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

  • Ádám Györkei

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

  • Eszter Ari

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

  • Viktória Lázár

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

  • István Nagy

    (Institute of Biochemistry, Biological Research Centre)

  • Mohan Babu

    (University of Regina)

  • Csaba Pál

    (Institute of Biochemistry, Biological Research Centre)

  • Balázs Papp

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

Abstract

Antimicrobial peptides (AMPs) are key effectors of the innate immune system and promising therapeutic agents. Yet, knowledge on how to design AMPs with minimal cross-resistance to human host-defense peptides remains limited. Here, we systematically assess the resistance determinants of Escherichia coli against 15 different AMPs using chemical-genetics and compare to the cross-resistance spectra of laboratory-evolved AMP-resistant strains. Although generalizations about AMP resistance are common in the literature, we find that AMPs with different physicochemical properties and cellular targets vary considerably in their resistance determinants. As a consequence, cross-resistance is prevalent only between AMPs with similar modes of action. Finally, our screen reveals several genes that shape susceptibility to membrane- and intracellular-targeting AMPs in an antagonistic manner. We anticipate that chemical-genetic approaches could inform future efforts to minimize cross-resistance between therapeutic and human host AMPs.

Suggested Citation

  • Bálint Kintses & Pramod K. Jangir & Gergely Fekete & Mónika Számel & Orsolya Méhi & Réka Spohn & Lejla Daruka & Ana Martins & Ali Hosseinnia & Alla Gagarinova & Sunyoung Kim & Sadhna Phanse & Bálint C, 2019. "Chemical-genetic profiling reveals limited cross-resistance between antimicrobial peptides with different modes of action," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13618-z
    DOI: 10.1038/s41467-019-13618-z
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