Antibiotic-resistant bacteria show widespread collateral sensitivity to antimicrobial peptides

Viktória Lázár, Ana Martins, Réka Spohn, Lejla Daruka, Gábor Grézal, Gergely Fekete, Mónika Számel, Pramod K. Jangir, Bálint Kintses, Bálint Csörgo, Ákos Nyerges, Ádám Györkei, András Kincses, A. Dér, Fruzsina R. Walter, Mária A. Deli, E. Urbán, Zsófia Hegedus, Gábor Olajos, Orsolya MéhiBalázs Bálint, István Nagy, T. Martinek, B. Papp, C. Pál

Research output: Article

50 Citations (Scopus)

Abstract

Antimicrobial peptides are promising alternative antimicrobial agents. However, little is known about whether resistance to small-molecule antibiotics leads to cross-resistance (decreased sensitivity) or collateral sensitivity (increased sensitivity) to antimicrobial peptides. We systematically addressed this question by studying the susceptibilities of a comprehensive set of 60 antibiotic-resistant Escherichia coli strains towards 24 antimicrobial peptides. Strikingly, antibiotic-resistant bacteria show a high frequency of collateral sensitivity to antimicrobial peptides, whereas cross-resistance is relatively rare. We identify clinically relevant multidrug-resistance mutations that increase bacterial sensitivity to antimicrobial peptides. Collateral sensitivity in multidrug-resistant bacteria arises partly through regulatory changes shaping the lipopolysaccharide composition of the bacterial outer membrane. These advances allow the identification of antimicrobial peptide-Antibiotic combinations that enhance antibiotic activity against multidrug-resistant bacteria and slow down de novo evolution of resistance. In particular, when co-Administered as an adjuvant, the antimicrobial peptide glycine-leucine-Amide caused up to 30-fold decrease in the antibiotic resistance level of resistant bacteria. Our work provides guidelines for the development of efficient peptide-based therapies of antibiotic-resistant infections.

Original languageEnglish
Pages (from-to)718-731
Number of pages14
JournalNature Microbiology
Volume3
Issue number6
DOIs
Publication statusPublished - jún. 1 2018

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ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Applied Microbiology and Biotechnology
  • Genetics
  • Microbiology (medical)
  • Cell Biology

Cite this

Lázár, V., Martins, A., Spohn, R., Daruka, L., Grézal, G., Fekete, G., Számel, M., Jangir, P. K., Kintses, B., Csörgo, B., Nyerges, Á., Györkei, Á., Kincses, A., Dér, A., Walter, F. R., Deli, M. A., Urbán, E., Hegedus, Z., Olajos, G., ... Pál, C. (2018). Antibiotic-resistant bacteria show widespread collateral sensitivity to antimicrobial peptides. Nature Microbiology, 3(6), 718-731. https://doi.org/10.1038/s41564-018-0164-0