Antibiotic-resistant bacteria show widespread collateral sensitivity to antimicrobial peptides.

Lazar, V [Lázár, Viktória (Molekuláris biológia), author] Institute of Biochemistry (MTA SZBK); Martins, A [Martins, Ana (mikrobiológia), author] Institute of Biochemistry (MTA SZBK); Spohn, R [Spohn, Réka (Biokémia), author] Institute of Biochemistry (MTA SZBK); Daruka, L [Daruka, Lejla (biokémia), author] Institute of Biochemistry (MTA SZBK); Grezal, G [Grézal, Gábor (molekuláris biológia), author] Institute of Biochemistry (MTA SZBK); Fekete, G [Fekete, Gergely (biokémia), author] Institute of Biochemistry (MTA SZBK); Szamel, M [Számel, Mónika (biokémia), author] Institute of Biochemistry (MTA SZBK); Jangir, PK [Jangir, Pramod Kumar (biokémia), author] Institute of Biochemistry (MTA SZBK); Kintses, B [Kintses, Bálint (biokémia), author] Institute of Biochemistry (MTA SZBK); Csorgo, B [Csörgő, Bálint (biokémia), author] Institute of Biochemistry (MTA SZBK); Nyerges, A [Nyerges, Ákos (biokémia), author] Institute of Biochemistry (MTA SZBK); Gyorkei, A [Györkei, Ádám (biokémia), author] Institute of Biochemistry (MTA SZBK); Kincses, A [Kincses, András (biofizika), author] Institute of Biophysics (MTA SZBK); Der, A [Dér, András (Biofizika), author] Institute of Biophysics (MTA SZBK); Walter, FR [Walter, Fruzsina (biofizika), author] Institute of Biophysics (MTA SZBK); Deli, MA [Deli, Mária Anna (Neurobiológia, vé...), author] Institute of Biophysics (MTA SZBK); Urban, E [Zsoldiné Urbán, Edit (orvostudomány), author] Department of Clinical Microbiology (USZ / ÁOK); Hegedus, Z [Hegedüs, Zsófia (gyógyszerkémia), author] Department of Pharmaceutical Analytics (USZ / FP); Olajos, G [Olajos, Gábor (Gyógyszerkémia), author] Department of Pharmaceutical Analytics (USZ / FP); Mehi, O [Méhi, Orsolya Katinka (biokémia), author] Institute of Biochemistry (MTA SZBK); Balint, B [Bálint, Balázs (biológia, bioinfo...), author]; Nagy, I [Nagy, István (Genomika, immunol...), author] Institute of Biochemistry (MTA SZBK); Martinek, TA [Martinek, Tamás (Gyógyszerkémia), author] Department of Pharmaceutical Analytics (USZ / FP); Papp, B [Papp, Balázs (biokémia), author] Institute of Biochemistry (MTA SZBK); Pal, C [Pál, Csaba (biokémia), author] Institute of Biochemistry (MTA SZBK)

English Scientific Article (Journal Article)
Published: NATURE MICROBIOLOGY 2058-5276 3 (6) pp. 718-731 2018
  • SJR Scopus - Applied Microbiology and Biotechnology: D1
Identifiers
Subjects:
    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.
    Citation styles: IEEEACMAPAChicagoHarvardCSL
    2019-10-16 11:55