Integrated evolutionary analysis reveals antimicrobial peptides with limited resistance

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, Anikó Faragó, László Bodai, Imre Földesi, Diána Kata, Gergely Maróti, Bernadett Pap, Roland WirthBalázs Papp, Csaba Pál

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2 Citations (Scopus)

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.

Original languageEnglish
Article number4538
JournalNature communications
Volume10
Issue number1
DOIs
Publication statusPublished - Dec 1 2019

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ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Spohn, R., Daruka, L., Lázár, V., Martins, A., Vidovics, F., Grézal, G., Méhi, O., Kintses, B., Számel, M., Jangir, P. K., Csörgő, B., Györkei, Á., Bódi, Z., Faragó, A., Bodai, L., Földesi, I., Kata, D., Maróti, G., Pap, B., ... Pál, C. (2019). Integrated evolutionary analysis reveals antimicrobial peptides with limited resistance. Nature communications, 10(1), [4538]. https://doi.org/10.1038/s41467-019-12364-6