Integrated evolutionary analysis reveals antimicrobial peptides with limited resistance

• Published in: Nature communications Vol. 10; no. 1; pp. 4538 - 13
• Main Authors: Spohn, Réka, Daruka, Lejla, Lázár, Viktória, Martins, Ana, Vidovics, Fanni, Grézal, Gábor, Méhi, Orsolya, Kintses, Bálint, Számel, Mónika, Jangir, Pramod K., Csörgő, Bálint, Györkei, Ádám, Bódi, Zoltán, Faragó, Anikó, Bodai, László, Földesi, Imre, Kata, Diána, Maróti, Gergely, Pap, Bernadett, Wirth, Roland, Papp, Balázs, Pál, Csaba
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 04.10.2019; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 38; 49; 631/181/2475; 631/326/1320; 631/61/338/22/1434; 64; Anti-Infective Agents - pharmacology; Antibiotic resistance; Antibiotics; Antiinfectives and antibacterials; Antimicrobial agents; Antimicrobial Cationic Peptides - pharmacology; Antimicrobial Cationic Peptides - therapeutic use; Antimicrobial peptides; Bacteria; Bacteria - drug effects; Bacteria - genetics; Bacterial Infections - drug therapy; Cecropin; Cross-resistance; Directed Molecular Evolution; Drug development; Drug Development - methods; Drug Resistance, Multiple, Bacterial - drug effects; Drug Resistance, Multiple, Bacterial - genetics; E coli; Evolution; Gene amplification; Genome, Bacterial - drug effects; Genome, Bacterial - genetics; Humanities and Social Sciences; Humans; Immune system; Innate immunity; Metagenomics; Microbial Sensitivity Tests; multidisciplinary; Mutation; Organic chemistry; Peptides; Plasmids; Plasmids - genetics; Point Mutation; Science; Science (multidisciplinary); Soil bacteria; Soil Microbiology; Soil microorganisms
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-019-12364-6

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. Antimicrobial peptides (AMPs) are emerging as drug candidates, but the risk of pathogen resistance is not well understood. Here, the authors investigate AMP resistance evolution in E. coli , finding physicochemical features that make AMPs less prone to resistance and no cross- or horizontally-acquired resistance.